Genetic analysis of the mammalian transforming growth factor-β superfamily

Endocrine Reviews

Volumn 23, Issue 6, 2002, Pages 787-823

  Chang, Hua ^a,b   Brown, Chester W ^a   Matzuk, Martin M ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVIN RECEPTOR; BONE MORPHOGENETIC PROTEIN; DNA BINDING PROTEIN; GROWTH FACTOR; LIGAND; NOGGIN; SMAD PROTEIN; TRANSFORMING GROWTH FACTOR ALPHA; TRANSFORMING GROWTH FACTOR BETA; ACTIVIN; GDNF PROTEIN, HUMAN; GDNF PROTEIN, MOUSE; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GROWTH PROMOTOR; INHIBIN; NERVE GROWTH FACTOR; PROTEIN SERINE THREONINE KINASE; SERINE THREONINE KINASE RECEPTOR; SERINE-THREONINE KINASE RECEPTOR; TRANSACTIVATOR PROTEIN; TRANSFORMING GROWTH FACTOR BETA RECEPTOR;

ANGIOGENESIS; BODY COMPOSITION; BONE DEVELOPMENT; CLEFT PALATE; CRANIOFACIAL DEVELOPMENT; EMBRYO; EMBRYO DEVELOPMENT; EYE DEVELOPMENT; GERM CELL; GONAD DEVELOPMENT; HEART DEVELOPMENT; HUMAN; KNOCKOUT MOUSE; LIGAND BINDING; MOUSE; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; PRIORITY JOURNAL; RECEPTOR BINDING; REVIEW; SEX DIFFERENTIATION; SIGNAL TRANSDUCTION; TOOTH DEVELOPMENT; TRANSGENIC MOUSE; ANIMAL; GENE EXPRESSION REGULATION; GENETICS; MOUSE MUTANT; PHYLOGENY; PHYSIOLOGY;

ACTIVINS; ANIMALS; BONE MORPHOGENETIC PROTEINS; DNA-BINDING PROTEINS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR; GROWTH SUBSTANCES; HUMANS; INHIBINS; MICE; MICE, KNOCKOUT; MICE, TRANSGENIC; NERVE GROWTH FACTORS; PHYLOGENY; PROTEIN-SERINE-THREONINE KINASES; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SMAD PROTEINS; TRANS-ACTIVATORS; TRANSFORMING GROWTH FACTOR BETA;

EID: 0036904895     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.2002-0003     Document Type: Review

References (424)

1. Hogan BL 1996 Bone morphogenetic proteins in development. Curr Opin Genet Dev 6:432-438
2. Kingsley DM 1994 The TGF-β superfamily: New members, new receptors, and new genetic tests of function in different organisms. Genes Dev 8:133-146
3. Massagué J 1998 TGF-β signal transduction. Annu Rev Biochem 67:753-791
4. Attisano L, Wrana JL 2002 Signal transduction by the TGF-β superfamily. Science 296:1646-1647
5. Zwijsen A, van Grunsven LA, Bosman EA, Collart C, Nelles L, Umans L, Van de Putte T, Wuytens G, Huylebroeck D, Verschueren K 2001 Transforming growth factor β signalling in vitro and in vivo: Activin ligand-receptor interaction, Smad5 in vasculogenesis, and repression of target genes by the δEF1/ZEB-related SIP1 in the vertebrate embryo. Mol Cell Endocrinol 180:13-24
6. Heldin C-H, Miyazono K, ten Dijke P 1997 TGF-β signalling from cell membrane to nucleus through SMAD proteins. Nature 390: 465-471
7. Wrana JL, Attisano L 1996 MAD-related proteins in TGF-β signalling. Trends Genet 12:493-496
8. Wotton D, Massague J 2001 Smad transcriptional corepressors in TGF β family signaling. Curr Top Microbiol Immunol 254:145-164
9. Dube JL, Wang P, Elvin J, Lyons KM, Celeste AJ, Matzuk MM 1998 The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol 12:1809-1817
10. Hogan BL 1996 Bone morphogenetic proteins: Multifunctional regulators of vertebrate development. Genes Dev 10:1580-1594
11. Padgett RW, Savage C, Das P 1997 Genetic and biochemical analysis of TGF β signal transduction. Biochem Biophys Res Commun 232:517-521
12. Gentry LE, Lioubin MN, Purchio AF, Marquardt H 1988 Molecular events in the processing of recombinant type 1 pre-pro-transforming growth factor β to the mature polypeptide. Mol Cell Biol 8:4162-4168
13. Lawrence DA, Pircher R, Kryceve-Martinerie C, Jullien P 1984 Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol 121:184-188
14. Dubois CM, Laprise MH, Blanchette F, Gentry LE, Leduc R 1995 Processing of transforming growth factor β 1 precursor by human furin convertase. J Biol Chem 270:10618-10624
15. Schultz-Cherry S, Lawler J, Murphy-Ullrich JE 1994 The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-β. J Biol Chem 269:26783-26788
16. Schultz-Cherry S, Ribeiro S, Gentry L, Murphy-Ullrich JE 1994 Thrombospondin binds and activates the small and large forms of latent transforming growth factor-β in a chemically defined system. J Biol Chem 269:26775-26782
17. Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, Pittet JF, Kaminski N, Garat C, Matthay MA, Rifkin DB, Sheppard D 1999 The integrin αvβ6 binds and activates latent TGF β 1: A mechanism for regulating pulmonary inflammation and fibrosis. Cell 96:319-328
18. Saharinen J, Hyytiainen M, Taipale J, Keski-Oja J 1999 Latent transforming growth factor-β binding proteins (LTBPs)-structural extracellular matrix proteins for targeting TGF-β action. Cytokine Growth Factor Rev 10:99-117
19. Wrana JL, Attisano L, Wieser R, Ventura F, Massague J 1994 Mechanism of activation of the TGF-β receptor. Nature 370:341-347
20. Souchelnytskyi S, ten Dijke P, Miyazono K, Heldin CH 1996 Phosphorylation of Ser165 in TGF-β type I receptor modulates TGF-β1-induced cellular responses. EMBO J 15:6231-6240
21. Wieser R, Wrana JL, Massague J 1995 GS domain mutations that constitutively activate T β R-I, the downstream signaling component in the TGF-β receptor complex. EMBO J 14:2199-2208
22. Attisano L, Carcamo J, Ventura F, Weis FM, Massague J, Wrana JL 1993 Identification of human activin and TGF β type I receptors that form heteromeric kinase complexes with type II receptors. Cell 75:671-680
23. Attisano L, Wrana JL, Montalvo E, Massague J 1996 Activation of signalling by the activin receptor complex. Mol Cell Biol 16:1066-1073
24. ten Dijke P, Yamashita H, Ichijo H, Franzen P, Laiho M, Miyazono K, Heldin CH 1994 Characterization of type I receptors for transforming growth factor-β and activin. Science 264:101-104
25. Yamashita H, ten Dijke P, Huylebroeck D, Sampath TK, Andries M, Smith JC, Heldin CH, Miyazono K 1995 Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects. J Cell Biol 130:217-226
26. Bauer H, Lele Z, Rauch GJ, Geisler R, Hammerschmidt M 2001 The type I serine/threonine kinase receptor Alk8/Lost-a-fin is required for Bmp2b/7 signal transduction during dorsoventral patterning of the zebrafish embryo. Development 128:849-858
27. Mintzer KA, Lee MA, Runke G, Trout J, Whitman M, Mullins MC 2001 Lost-a-fin encodes a type I BMP receptor, Alk8, acting maternally and zygotically in dorsoventral pattern formation. Development 128:859-869
28. Payne TL, Postlethwait JH, Yelick PC 2001 Functional characterization and genetic mapping of alk8. Mech Dev 100:275-289
29. Bassing CH, Yingling JM, Howe DJ, Wang T, He WW, Gustafson ML, Shah P, Donahoe PK, Wang XF 1994 A transforming growth factor β type I receptor that signals to activate gene expression. Science 263:87-89
30. Ebner R, Chen RH, Lawler S, Zioncheck T, Derynck R 1993 Determination of type I receptor specificity by the type II receptors for TGF-β or activin. Science 262:900-902
31. Franzen P, ten Dijke P, Ichijo H, Yamashita H, Schulz P, Heldin CH, Miyazono K 1993 Cloning of a TGF β type I receptor that forms a heteromeric complex with the TGF β type II receptor. Cell 75: 681-692
32. Liu F, Ventura F, Doody J, Massague J 1995 Human type II receptor for bone morphogenic proteins (BMPs): Extension of the two-kinase receptor model to the BMPs. Mol Cell Biol 15:3479-3486
33. Nishitoh H, Ichijo H, Kimura M, Matsumoto T, Makishima F, Yamaguchi A, Yamashita H, Enomoto S, Miyazono K 1996 Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5. J Biol Chem 271:21345-21352
34. Nohno T, Ishikawa T, Saito T, Hosokawa K, Noji S, Wolsing DH, Rosenbaum JS 1995 Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors. J Biol Chem 270:22522-22526
35. Rosenzweig BL, Imamura T, Okadome T, Cox GN, Yamashita H, ten Dijke P, Heldin CH, Miyazono K 1995 Cloning and characterization of a human type II receptor for bone morphogenetic proteins. Proc Natl Acad Sci USA 92:7632-7636
36. Wrana J, Pawson T 1997 Signal transduction. Mad about SMADs. Nature 388:28-29
37. Cheifetz S, Weatherbee JA, Tsang ML, Anderson JK, Mole JE, Lucas R, Massague J 1987 The transforming growth factor-β system, a complex pattern of cross-reactive ligands and receptors. Cell 48:409-415
38. Gougos A, Letarte M 1990 Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem 265:8361-8364
39. Lastres P, Letamendia A, Zhang H, Rius C, Almendro N, Raab U, Lopez LA, Langa C, Fabra A, Letarte M, Bernabeu C 1996 Endoglin modulates cellular responses to TGF-β 1. J Cell Biol 133:1109-1121
40. Cheifetz S, Massague J 1991 Isoform-specific transforming growth factor-β binding proteins with membrane attachments sensitive to phosphatidylinositol-specific phospholipase C. J Biol Chem 266: 20767-20772
41. Segarini PR, Rosen DM, Seyedin SM 1989 Binding of transforming growth factor-β to cell surface proteins varies with cell type. Mol Endocrinol 3:261-272
42. Lewis KA, Gray PC, Blount AL, MacConell LA, Wiater E, Bilezikjian LM, Vale W 2000 Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature 404:411-414
43. Chong H, Pangas SA, Bemard DJ, Wang E, Gitch J, Chen W, Draper LB, Cox ET, Woodruff TK 2000 Structure and expression of a membrane component of the inhibin receptor system. Endocrinology 141:2600-2607
44. Chapman SC, Woodruff TK 2001 Modulation of activin signal transduction by inhibin b and inhibin-binding protein (INhBP). Mol Endocrinol 15:668-679
45. Bernard DJ, Woodruff TK 2001 Inhibin binding protein in rats: Alternative transcripts and regulation in the pituitary across the estrous cycle. Mol Endocrmol 15:654-667
46. Sekelsky JJ, Newfeld SJ, Raftery LA, Chartoff EH, Gelbart WM 1995 Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics 139:1347-1358
47. Savage C, Das P, Finelli AL, Townsend SR, Sun CY, Baird SE, Padgett RW 1996 Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor β pathway components. Proc Natl Acad Sci USA 93:790-794
48. Derynck R, Gelbart WM, Harland RM, Heldin CH, Kern SE, Massague J, Melton DA, Mlodzik M, Padgett RW, Roberts AB, Smith J, Thomsen GH, Vogelstein B, Wang XF 1996 Nomenclature: Vertebrate mediators of TGFβ family signals. Cell 87:173
49. Massague J, Chen YG 2000 Controlling TGF-β signaling. Genes Dev 14:627-644
50. Macleod K 2000 Tumor suppressor genes. Curr Opin Genet Dev 10:81-93
51. Reiss M 1999 TGF-β and cancer. Microbes Infect 1:1327-1347
52. Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, Kern SE 1996 DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 271:350-353
53. Wrana JL 1998 TGF-β receptors and signalling mechanisms. Miner Electrolyte Metab 24:131-135
54. Graff JM, Bansal A, Melton DA 1996 Xenopus mad proteins transduce distinct subsets of signals for the TGF β superfamily. Cell 85:479-487
55. Suzuki A, Chang C, Yingling JM, Wang XF, Hemmati-Brivanlou A 1997 Smad5 induces ventral fates in Xenopus embryo. Dev Biol 184:402-405
56. Thomsen GH 1996 Xenopus mothers against decapentaplegic is an embryonic ventralizing agent that acts downstream of the BMP-2/4 receptor. Development 122:2359-2366
57. Eppert K, Scherer SW, Ozcelik H, Pirone R, Hoodless P, Kim H, Tsui LC, Bapat B, Gallinger S, Andrulis IL, Thomsen GH, Wrana JL, Attisano L 1996 MADR2 maps to 18q21 and encodes a TGFβ-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell 86:543-552
58. Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin CH, Miyazono K, ten Dijke P 1997 TGF-β receptor-mediated signalling through Smad2, Smad3 and Smad4. EMBO J 16:5353-5362
59. Zhang Y, Feng X, We R, Derynck R 1996 Receptor-associated Mad homologues synergize as effectors of the TGF-β response. Nature 383:168-172
60. Hoodless PA, Haerry T, Abdollah S, Stapleton M, O'Connor MB, Attisano L, Wrana JL 1996 MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell 85:489-500
61. Kretzschmar M, Liu F, Hata A, Doody J, Massague J 1997 The TGF-β family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase. Genes Dev 11: 984-995
62. Liu F, Hata A, Baker JC, Doody J, Carcamo J, Harland RM, Massague J 1996 A human Mad protein acting as a BMP-regulated transcriptional activator. Nature 381:620-623
63. Watanabe TK, Suzuki M, Omori Y, Hishigaki H, Horie M, Kanemoto N, Fujiwara T, Nakamura Y, Takahashi E 1997 Cloning and characterization of a novel member of the human Mad gene family (MADH6). Genomics 42:446-451
64. Howell M, Itoh F, Pierreux CE, Valgeirsdottir S, Itoh S, ten Dijke P, Hill CS 1999 Xenopus Smad4β is the co-Smad component of developmentally regulated transcription factor complexes responsible for induction of early mesodermal genes. Dev Biol 214:354-369
65. Masuyama N, Hanafusa H, Kusakabe M, Shibuya H, Nishida E 1999 Identification of two Smad4 proteins in Xenopus. Their common and distinct properties. J Biol Chem 274:12163-12170
66. Das P, Maduzia LL, Wang H, Finelli AL, Cho SH, Smith MM, Padgett RW 1998 The Drosophila gene Medea demonstrates the requirement for different classes of Smads in dpp signaling. Development 125:1519-1528
67. Hudson JB, Podos SD, Keith K, Simpson SL, Ferguson EL 1998 The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4. Development 125:1407-1420
68. Wisotzkey RG, Mehra A, Sutherland DJ, Dobens LL, Liu X, Dohrmann C, Attisano L, Raftery LA 1998 Medea is a Drosophila Smad4 homolog that is differentially required to potentiate DPP responses. Development 125:1433-1445
69. Hata A, Lo RS, Wotton D, Lagna G, Massague J 1997 Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4. Nature 388:82-87
70. Lagna G, Hata A, Hemmati-Brivanlou A, Massague J 1996 Partnership between DPC4 and SMAD proteins in TGF-β signalling pathways. Nature 383:832-836
71. Zhang Y, Musci T, Derynck R 1997 The tumor suppressor Smad4/DPC 4 as a central mediator of Smad function. Curr Biol 7:270-276
72. Ishisaki A, Yamato K, Hashimoto S, Nakao A, Tamaki K, Nonaka K, ten Dijke P, Sugino H, Nishihara T 1999 Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and activinmediated growth arrest and apoptosis in B cells. J Biol Chem 274:13637-13642
73. Ishisaki A, Yamato K, Nakao A, Nonaka K, Ohguchi M, ten Dijke P, Nishihara T 1998 Smad7 is an activin-inducible inhibitor of activin-induced growth arrest and apoptosis in mouse B cells. J Biol Chem 273:24293-24296
74. Souchelnytskyi S, Nakayama T, Nakao A, Moren A, Heldin CH, Christian JL, ten Dijke P 1998 Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-β receptors. J Biol Chem 273:25364-25370
75. Kogawa K, Nakamura T, Sugino K, Takio K, Titani K, Sugino H 1991 Activin-binding protein is present in pituitary. Endocrinology 128:1434-1440
76. Shimonaka M, Inouye S, Shimasaki S, Ling N 1991 Follistatin binds to both activin and inhibin through the common subunit. Endocrinology 128:3313-3315
77. Iemura S, Yamamoto TS, Takagi C, Uchiyama H, Natsume T, Shimasaki S, Sugino H, Ueno N 1998 Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell lates in early Xenopus embryo. Proc Natl Acad Sci USA 95:9337-9342
78. Piccolo S, Sasai Y, Lu B, De Robertis EM 1996 Dorsoventral patterning in Xenopus: Inhibition of ventral signals by direct binding of chordin to BMP-4. Cell 86:589-598
79. Zimmerman LB, De Jesus-Escobar JM, Harland RM 1996 The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Cell 86:599-606
80. Bornstein P 1995 Diversity of function is inherent in matricellular proteins: An appraisal of thrombospondin 1. J Cell Biol 130:503-506
81. Lahav J 1993 The functions of thrombospondin and its involvement in physiology and pathophysiology. Biochim Biophys Acta 1182: 1-14
82. Murphy-Ullrich JE, Schultz-Cherry S, Hook M 1992 Transforming growth factor-β complexes with thrombospondin. Mol Biol Cell 3:181-188
83. Souchelnitskiy S, Chambaz EM, Feige JJ 1995 Thrombospondins selectively activate one of the two latent forms of transforming growth factor-β present in adrenocortical cell-conditioned medium. Endocrinology 136:5118-5126
84. Crawford SE, Stellmach V, Murphy-Ullrich JE, Ribeiro SM, Lawler J, Hynes RO, Boivin GP, Bouck N 1998 Thrombospondin-1 is a major activator of TGF-β1 in vivo. Cell 93:1159-1170
85. Okadome T, Oeda E, Saitoh M, Ichijo H, Moses HL, Miyazono K, Kawabata M 1996 Characterization of the interaction of FKBP12 with the transforming growth factor-β type I receptor in vivo. J Biol Chem 271:21687-21690
86. Wang T, Li BY, Danielson PD, Shah PC, Rockwell S, Lechleider RJ, Martin J, Manganaro T, Donahoe PK 1996 The immunophilin FKBP12 functions as a common inhibitor of the TGF β family type I receptors. Cell 86:435-444
87. Chen YG, Liu F, Massague J 1997 Mechanism of TGFβ receptor inhibition by FKBP12. EMBO J 16:3866-3876
88. Bassing CH, Shou W, Muir S, Heitman J, Matzuk MM, Wang XF 1998 FKBP12 is not required for the modulation of transforming growth factor β receptor I signaling activity in embryonic fibroblasts and thymocytes. Cell Growth Differ 9:223-228
89. Charng MJ, Kinnunen P, Hawker J, Brand T, Schneider MD 1996 FKBP-12 recognition is dispensable for signal generation by type I transforming growth factor-β receptors. J Biol Chem 271:22941-22944
90. Shou W, Aghdasi B, Armstrong DL, Guo Q, Bao S, Charng M-J, Mathews LS, Schneider MD, Hamilton SL, Matzuk MM 1998 Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12. Nature 391:489-492
91. Aghdasi B, Ye K, Resnick A, Huang A, Ha HC, Guo X, Dawson TM, Dawson VL, Snyder SH 2001 FKBP12, the 12-kDa FK506-binding protein, is a physiologic regulator of the cell cycle. Proc Natl Acad Sci USA 98:2425-2430
92. Chen RH, Miettinen PJ, Maruoka EM, Choy L, Derynck R 1995 A WD-domain protein that is associated with and phosphorylated by the type II TGF-β receptor. Nature 377:548-552
93. Choy L, Derynck R 1998 The type II transforming growth factor (TGF)-β receptor-interacting protein TRIP-1 acts as a modulator of the TGF-β response. J Biol Chem 273:31455-31462
94. Tsukazaki T, Chiang TA, Davison AF, Attisano L, Wrana JL 1998 SARA, a FYVE domain protein that recruits Smad2 to the TGFβ receptor. Cell 95:779-791
95. Yamaguchi K, Shirakabe K, Shibuya H, Irie K, Oishi I, Ueno N, Taniguchi T, Nishida E, Matsumoto K 1995 Identification of a member of the MAPKKK family as a potential mediator of TGF-β signal transduction. Science 270:2008-2011
96. Monzen K, Shiojima I, Hiroi Y, Kudoh S, Oka T, Takimoto E, Hayashi D, Hosoda T, Habara-Ohkubo A, Nakaoka T, Fujita T, Yazaki Y, Komuro I 1999 Bone morphogenetic proteins induce cardiomyocyte differentiation through the mitogen-activated protein kinase kinase kinase TAK1 and cardiac transcription factors Csx/Nkx-2.5 and GATA-4. Mol Cell Biol 19:7096-7105
97. Shibuya H, Iwata H, Masuyama N, Gotoh Y, Yamaguchi K, Irie K, Matsumoto K, Nishida E, Ueno N 1998 Role of TAK1 and TAB1 in BMP signaling in early Xenopus development. EMBO J 17:1019-1028
98. Kishimoto K, Matsumoto K, Ninomiya-Tsuji J 2000 TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop J Biol Chem 275:7359-7364
99. Sakurai H, Miyoshi H, Mizukami J, Sugita T 2000 Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1. FEBS Lett 474:141-145
100. Shibuya H, Yamaguchi K, Shirakabe K, Tonegawa A, Gotoh Y, Ueno N, Irie K, Nishida E, Matsumoto K 1996 TAB1: An activator of the TAK1 MAPKKK in TGF-β signal transduction. Science 272: 1179-1182
101. Yamaguchi K, Nagai S, Ninomiya-Tsuji J, Nishita M, Tamai K, Irie K, Ueno N, Nishida E, Shibuya H, Matsumoto K 1999 XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway. EMBO J 18:179-187
102. Attisano L, Wrana JL 2000 Smads as transcriptional co-modulators. Curr Opin Cell Biol 12:235-243
103. Janknecht R, Wells NJ, Hunter T 1998 TGF-β-stimulated cooperation of smad proteins with the coactivators CBP/p300. Genes Dev 12:2114-2119
104. Feng XH, Zhang Y, Wu RY, Derynck R 1998 The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for smad3 in TGF-β-induced transcriptional activation. Genes Dev 12:2153-2163
105. Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC, Masuno M, Tommerup N, van Ommen GJ, Goodman RH, Peters DJ, Breuning MH 1995 Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376:348-351
106. Muraoka M, Konishi M, Kikuchi-Yanoshita R, Tanaka K, Shitara N, Chong JM, Iwama T, Miyaki M 1996 p300 Gene alterations in colorectal and gastric carcinomas. Oncogene 12:1565-1569
107. Oike Y, Hata A, Mamiya T, Kaname T, Noda Y, Suzuki M, Yasue H, Nabeshima T, Araki K, Yamamura K 1999 Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: Implications for a dominant-negative mechanism. Hum Mol Genet 8:387-396
108. Tanaka Y, Naruse I, Maekawa T, Masuya H, Shiroishi T, Ishii S 1997 Abnormal skeletal patterning in embryos lacking a single Cbp allele: A partial similarity with Rubinstein-Taybi syndrome. Proc Natl Acad Sci USA 94:10215-10220
109. Kung AL, Rebel VI, Bronson RT, Ch'ng LE, Sieff CA, Livingston DM, Yao TP 2000 Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. Genes Dev 14:272-277
110. Yao TP, Oh SP, Fuchs M, Zhou ND, Ch'ng LE, Newsome D, Bronson RT, Li E, Livingston DM, Eckner R 1998 Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93:361-372
111. Chen X, Rubock MJ, Whitman M 1996 A transcriptional partner for MAD proteins in TGF-β signalling. Nature 383:691-696
112. Hoodless PA, Pye M, Chazaud C, Labbe E, Attisano L, Rossant J, Wrana JL 2001 FoxH1 (Fast) functions to specify the anterior primitive streak in the mouse. Genes Dev 15:1257-1271
113. Kim RH, Wang D, Tsang M, Martin J, Huff C, de Caestecker MP, Parks WT, Meng X, Lechleider RJ, Wang T, Roberts AB 2000 A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-β signal transduction. Genes Dev 14:1605-1616
114. Wotton D, Lo RS, Lee S, Massague J 1999 A Smad transcriptional corepressor. Cell 97:29-39
115. Melhuish TA, Gallo CM, Wotton D 2001 TGIF2 interacts with histone deacetylase 1 and represses transcription. J Biol Chem 276:32109-32114
116. Verschueren K, Remacle JE, Collart C, Kraft H, Baker BS, Tylzanowski P, Nelles L, Wuytens G, Su MT, Bodmer R, Smith JC, Huylebroeck D 1999 SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5′-CACCT sequences in candidate target genes. J Biol Chem 274:20489-20498
117. Gripp KW, Wotton D, Edwards MC, Roessler E, Ades L, Meinecke P, Richieri-Costa A, Zackai EH, Massague J, Muenke M, Elledge SJ 2000 Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination. Nat Genet 25:205-208
118. Wakamatsu N, Yamada Y, Yamada K, Ono T, Nomura N, Taniguchi H, Kitoh H, Mutoh N, Yamanaka T, Mushiake K, Kato K, Sonta S, Nagaya M 2001 Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease. Nat Genet 27:369-370
119. Yamada K, Yamada Y, Nomura N, Miura K, Wakako R, Hayakawa C, Matsumoto A, Kumagai T, Yoshimura I, Miyazaki S, Kato K, Sonta S, Ono H, Yamanaka T, Nagaya M, Wakamatsu N 2001 Nonsense and frameshift mutations in ZFHXIB, encoding Smad-interacting protein 1, cause a complex developmental disorder with a great variety of clinical features. Am J Hum Genet 69:1178-1185
120. Amiel J, Espinosa-Parrilla Y, Steffann J, Gosset P, Pelet A, Prieur M, Boute O, Choiset A, Lacombe D, Philip N, Le Merrer M, Tanaka H, Till M, Touraine R, Toutain A, Vekemans M, Munnich A, Lyonnet S 2001 Large-scale deletions and SMADIP1 truncating mutations in syndromic Hirschsprung disease with involvement of midline structures. Am J Hum Genet 69:1370-1377
121. Cacheux V, Dastot-Le Moal F, Kaariainen H, Bondurand N, Rintala R, Boissier B, Wilson M, Mowat D, Goossens M 2001 Loss-of-function mutations in SIP1 Smad interacting protein 1 result in a syndromic Hirschsprung disease. Hum Mol Genet 10: 1503-1510
122. Stroschein SL, Wang W, Zhou S, Zhou Q, Luo K 1999 Negative feedback regulation of TGF-β signaling by the SnoN oncoprotein. Science 286:771-774
123. Sun Y, Liu X, Eaton EN, Lane WS, Lodish HF, Weinberg RA 1999 Interaction of the Ski oncoprotein with Smad3 regulares TGF-β signaling. Mol Cell 4:499-509
124. Bonni S, Wang HR, Causing CG, Kavsak P, Stroschein SL, Luo K, Wrana JL 2001 TGF-β induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nat Cell Biol 3:587-595
125. Stroschein SL, Bonni S, Wrana JL, Luo K 2001 Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN. Genes Dev 15:2822-2836
126. Podos SD, Hanson KK, Wang YC, Ferguson EL 2001 The D Smurf ubiquitin-protein ligase restricts BMP signaling spatially and temporally during Drosophila embryogenesis. Dev Cell 1:567-578
127. Zhang Y, Chang C, Gehling DJ, Hemmati-Brivanlou A, Derynck R 2001 Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase. Proc Natl Acad Sci USA 98:974-979
128. Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, Thomsen GH, Wrana JL 2000 Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF β receptor for degradation. Mol Cell 6:1365-1375
129. Zhu H, Kavsak P, Abdollah S, Wrana JL, Thomsen GH 1999 A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature 400:687-693
130. Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, Miyazono K 2001 Smurf1 interacts with transforming growth factor-β type I receptor through Smad7 and induces receptor degradation. J Biol Chem 276:12477-12480
131. Berk M, Desai SY, Heyman HC, Colmenares C 1997 Mice lacking the ski proto-oncogene have defects in neurulation, craniofacial, patterning, and skeletal muscle development. Genes Dev 11:2029-2039
132. Colmenares C, Heilstedt HA, Shaffer LG, Schwartz S, Berk M, Murray JC, Stavnezer E 2002 Loss of the SKI proto-oncogene in individuais affected with 1p36 deletion syndrome is predicted by strain-dependent defects in Ski-/- mice. Nat Genet 30:106-109
133. Shinagawa T, Nomura T, Colmenares C, Ohira M, Nakagawara A, Ishii S 2001 Increased susceptibility to tumorigenesis of ski-deficient heterozygous mice. Oncogene 20:8100-8108
134. Beddington RS, Robertson EJ 1999 Axis development and early asymmetry in mammals. Cell 96:195-209
135. Hogan B, Beddington R, Costantini F, Lacy E 1994 Manipulating the Mouse Embryo: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press
136. Conlon FL, Lyons KM, Takaesu N, Barth KS, Kispert A, Herrmann B, Robertson EJ 1994 A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. Development 120:1919-1928
137. Meno C, Gritsman K, Ohishi S, Ohfuji Y, Heckscher E, Mochida K, Shimono A, Kondoh H, Talbot WS, Robertson EJ, Schier AF, Hamada H 1999 Mouse lefty2 and zebrafish antivin are feedback inhibitors of nodal signaling during vertebrate gastrulation. Mol Cell 4:287-298
138. Gu Z, Reynolds EM, Song J, Lei H, Feijen A, Yu L, He W, MacLaughlin DT, van den Eijnden-van Raaij J, Donahoe PK, Li E 1999 The type I serine/threonine kinase receptor ActRIA (ALK2) is required for gastrulation of the mouse embryo. Development 126:2551-2561
139. Mishina Y, Crombie R, Bradley A, Behringer RR 1999 Multiple roles for activin-like kinase-2 signaling during mouse embryogenesis. Dev Biol 213:314-326
140. Beppu H, Kawabata M, Hamamoto T, Chytil A, Minowa O, Noda T, Miyazono K 2000 BMP type II receptor is required for gastrulation and early development of mouse embryos. Dev Biol 221: 249-258
141. Mishina Y, Suzuki A, Ueno N, Behringer RR 1995 Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes Dev 9:3027-3037
142. Matzuk MM, Kumar TR, Bradley A 1995 Different phenotypes for mice deficient in either activins or activin receptor type II. Nature 374:356-360
143. Oh SP, Li E 1997 The signaling pathway mediated by the type IIB activin receptor controls axial patterning and lateral asymmetry in the mouse. Genes Dev 11:1812-1826
144. Song J, Oh SP, Schrewe H, Nomura M, Lei H, Okano M, Gridley T, Li E 1999 The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice. Dev Biol 213:157-169
145. Nomura M, Li E 1998 Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature 393:786-790
146. Ying Y, Zhao GQ 2001 Cooperation of endoderm-derived BMP2 and extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse. Dev Biol 232:484-492
147. Ying Y, Liu X-M, Marble A, Lawson KA, Zhao G-Q 2000 Requirement of BMP8b for the generation of primordial germ cells in the mouse. Mol Endocrinol 14:1053-1063
148. Solloway MJ, Robertson EJ 1999 Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup. Development 126:1753-1768
149. Chang H, Huylebroeck D, Verschueren K, Guo Q, Matzuk MM, Zwijsen A 1999 Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development 126: 1631-1642
150. Yang X, Castilla LH, Xu X, Li C, Gotay J, Weinstein M, Liu PP, Deng CX 1999 Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development 126:1571-1580
151. Tremblay KD, Dunn NR, Robertson EJ 2001 Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation. Development 128:3609-3621
152. Lechleider RJ, Ryan JL, Garrett L, Eng C, Deng C, Wynshaw-Boris A, Roberts AB 2001 Targeted mutagenesis of Smad1 reveals an essential role in chorioallantoic fusion. Dev Biol 240:157-167
153. Paria BC, Ma W, Tan J, Raja S, Das SK, Dey SK, Hogan BL 2001 Cellular and molecular responses of the uterus to embryo implantation can be elicited by locally applied growth factors. Proc Natl Acad Sci USA 98:1047-1052
154. Kaufman MH 1992 The Atlas of Mouse Development. London: Academic Press
155. Harvey RP 2002 Molecular determinants of cardiac development and congenital heart diseases. In: Rossant J, Tam PP, eds. Mouse Development: Patterning, Morphogenesis and Organogenesis. New York: Academic Press, 331-370
156. Zhang H, Bradley A 1996 Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122:2977-2986
157. Kingsley DM, Bland AE, Grubber JM, Marker PC, Russell LB, Copeland NG, Jenkins NA 1992 The mouse short ear skeletal morphogenesis locus is associated with defects in a bone morphogenetic member of the TGF β superfamily. Cell 71:399-410
158. Solloway MJ, Dudley AT, Bikoff EK, Lyons KM, Hogan BLM, Robertson EJ 1998 Mice lacking Bmp6 function. Dev Genet 22: 321-339
159. Dudley AT, Lyons KM, Robertson EJ 1995 A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev 9:2795-2807
160. Luo G, Hofmann C, Bronckers AL, Sohocki M, Bradley A, Karsenty G 1995 BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev 9:2808-2820
161. Kim RY, Robertson EJ, Solloway MJ 2001 Bmp6 and Bmp7 are required for cushion formation and septation in the developing mouse heart. Dev Biol 235:449-466
162. Boyer AS, Ayerinskas II, Vincent EB, McKinney LA, Weeks DL, Runyan RB 1999 TGFβ2 and TGFβ3 have separate and sequential activities during epithelial-mesenchymal cell transformation in the embryonic heart. Dev Biol 208:530-545
163. Brown CB, Boyer AS, Runyan RB, Barnett JV 1996 Antibodies to the type II TGFβ receptor block cell activation and migration during atrioventricular cushion transformation in the heart. Dev Biol 174: 248-257
164. Brown CB, Boyer AS, Runyan RB, Barnett JV 1999 Requirement of type III TGF-β receptor for endocardial cell transformation in the heart. Science 283:2080-2082
165. Akhurst RJ, Lehnert SA, Faissner A, Duffie E 1990 TGF β in murine morphogenetic processes: The early embryo and cardiogenesis. Development 108:645-656
166. Mahmood R, Flanders KC, Morriss-Kay GM 1992 Interactions between retinoids and TGFβs in mouse morphogenesis. Development 115:67-74
167. Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ 1995 Defective haematopoiesis and vasculogenesis in transforming growth factor-β 1 knock out mice. Development 121: 1845-1854
168. Dickson MC, Slager HG, Duffie E, Mummery CL, Akhurst RJ 1993 RNA and protein localisations of TGF β 2 in the early mouse embryo suggest an involvement in cardiac development. Development 117:625-639
169. Sanford LP, Ormsby I, Gittenberger-de Groot AC, Sariola H, Friedman R, Boivin GP, Cardell EL, Doetschman T 1997 TGFβ2 knockout mice have multiple developmental defects that are non-overlapping with other TGFβ knockout phenotypes. Development 124:2659-2670
170. Gaussin V, Van de Putte T, Mishina Y, Hanks MC, Zwijsen A, Huylebroeck D, Behringer RR, Schneider MD 2002 Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3. Proc Natl Acad Sci USA 99:2878-2883
171. Charng MJ, Frenkel PA, Lin Q, Yamada M, Schwartz RJ, Olson EN, Overbeek P, Schneider MD, Yumada M 1998 A constitutive mutation of ALK5 disrupts cardiac looping and morphogenesis in mice. Dev Biol 199:72-79
172. Chang H, Zwijsen A, Vogel H, Huylebroeck D, Matzuk MM 2000 Smad5 is essential for left-right asymmetry in mice. Dev Biol 219: 71-78
173. Galvin KM, Donovan MJ, Lynch CA, Meyer RI, Paul RJ, Lorenz JN, Fairchild-Huntress V, Dixon KL, Dunmore JH, Gimbrone Jr MA, Falb D, Huszar D 2000 A role for smad6 in development and homeostasis of the cardiovascular system. Nat Genet 24:171-174
174. Lane KB, Machado RD, Pauciulo MW, Thomson JR, Phillips III JA, Loyd JE, Nichols WC, Trembath RC 2000 Heterozygous germllne mutations in BMPR2, encoding a TGF-β receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet 26:81-84
175. Levin M, Mercola M 1998 The compulsion of chirality: Toward an understanding of left-right asymmetry. Genes Dev 12:763-769
176. Ramsdell AF, Yost HJ 1998 Molecular mechanisms of vertebrate left-right development. Trends Genet 14:459-465
177. Tamura K, Yonei-Tamura S, Belmonte JC 1999 Molecular basis of left-right asymmetry. Dev Growth Differ 41:645-656
178. Yost HJ 1998 Left-right development in Xenopus and zebrafish. Semin Cell Dev Biol 9:61-66
179. Varlet I, Collignon J, Robertson EJ 1997 Nodal expression in the primitive endoderm is required for specification of the anterior axis during mouse gastrulation. Development 124:1033-1044
180. Zhou X, Sasaki H, Lowe L, Hogan BL, Kuehn MR 1993 Nodal is a novel TGF-β-like gene expressed in the mouse node during gastrulation. Nature 361:543-547
181. Lowe LA, Supp DM, Sampath K, Yokoyama T, Wright CV, Potter SS, Overbeek P, Kuehn MR 1996 Conserved left-right asymmetry of nodal expression and alterations in murine situs inversus. Nature 381:158-161
182. Pagan-Westphal SM, Tabin CJ 1998 The transfer of left-right positional information during chick embryogenesis. Cell 93:25-35
183. Meno C, Ito Y, Saijoh Y, Matsuda Y, Tashiro K, Kuhara S, Hamada H 1997 Two closely-related left-right asymmetrically expressed genes, lefty-1 and lefty-2: Their distinct expression domains, chromosomal linkage and direct neuralizing activity in Xenopus embryos. Genes Cells 2:513-524
184. Meno C, Shimono A, Saijoh Y, Yashiro K, Mochida K, Ohishi S, Noji S, Kondoh H, Hamada H 1998 Lefty-1 is required for left-right determination as a regulator of lefty-2 and nodal. Cell 94:287-297
185. Rankin CT, Bunton T, Lawler AM, Lee SJ 2000 Regulation of left-right patterning in mice by growth/differentiation factor-1. Nat Genet 24:262-265
186. Lee SJ 1991 Expression of growth/differentiation factor 1 in the nervous system: Conservation of a bicistronic structure. Proc Natl Acad Sci USA 88:4250-4254
187. Risau W, Flamme I 1995 Vasculogenesis. Annu Rev Cell Dev Biol 11:73-91
188. Beck Jr L, D'Amore PA 1997 Vascular development: Cellular and molecular regulation. FASEB J 11:365-373
189. Pepper MS 1997 Transforming growth factor-β: Vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev 8:21-43
190. Kulkarni AB, Huh CG, Becker D, Geiser A, Lyght M, Flanders KC, Roberts AB, Sporn MB, Ward JM, Karlsson S 1993 Transforming growth factor β 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 90:770 -774
191. Martin JS, Dickson MC, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ 1995 Analysis of homozygous TGF β 1 null mouse embryos demonstrates defects in yolk sac vasculogenesis and hematopoiesis. Ann N Y Acad Sci 752:300-308
192. Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D, Annunziata N, Doetschman T 1992 Targeted disruption of the mouse transforming growth factor-β 1 gene results in multifocal inflammatory disease. Nature 359:693-699
193. Oshima M, Oshima H, Taketo MM 1996 TGF-β receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Dev Biol 179:297-302
194. Guttmacher AE, Marchuk DA, White Jr RI 1995 Hereditary hemorrhagic telangiectasia. N Engl J Med 333:918-924
195. Cheifetz S, Bellon T, Cales C, Vera S, Bernabeu C, Massague J, Letarte M 1992 Endoglin is a component of the transforming growth factor-β receptor system in human endothelial cells. J Biol Chem 267:19027-19030
196. McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE, Helmbold EA, Markel DS, McKinnon WC, Murrell J, McCormick MK, Pericak-Vance MA, Heutink P, Oostra BA, Haitjerna T, Westerman CJJ, Porteous ME, Guttmacher AE, Letarte M, Marchuk DA 1994 Endoglin, a TGF-β binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 8:345-351
197. Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, Boak BB, Wendel DP 1999 Defecfive angiogenesis in mice lacking endoglin. Science 284:1534-1537
198. Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E 2000 Activin receptor-like kinase 1 modulates transforming growth factor-β 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci USA 97:2626-2631
199. Urness LD, Sorensen LK, Li DY 2000 Arteriovenous malformations in mice lacking activin receptor-like kinase-1. Nat Genet 26: 328-331
200. Macias-Silva M, Hoodless PA, Tang SJ, Buchwald M, Wrana JL 1998 Specific activation of Smad1 signaling pathways by the BMP7 type I receptor. J Biol Chem 273:25628-25636
201. Chen YG, Massague J 1999 Smadl1 recognition and activation by the ALK1 group of transforming growth factor-β family receptors. J Biol Chem 274:3672-3677
202. Larsson J, Goumans MJ, Sjostrand LJ, van Rooijen MA, Ward D, Leveen P, Xu X, ten Dijke P, Mummery CL, Karlsson S 2001 Abnormal angiogenesis bur intact hematopoietic potential in TGF-β type I receptor-deficient mice. EMBO J 20:1663-1673
203. Goumans MJ, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P, ten Dijke P 2002 Balancing the activation state of the endothelium via two distinct TGF-β type I receptors. EMBO J 21:1743-1753
204. Ferguson MW 1994 Craniofacial malformations: Towards a molecular understanding. Nat Genet 6:329-330
205. Kaartinen V, Voncken JW, Shuler C, Warburton D, Bu D, Heisterkamp N, Groffen J 1995 Abnormal lung development and cleft palate in mice lacking TGF-β 3 indicates defects of epithelial-mesenchymal interaction. Nat Genet 11:415-421
206. Proetzel G, Pawlowski SA, Wiles MV, Yin M, Boivin GP, Howles PN, Ding J, Ferguson MW, Doetschman T 1995 Transforming growth factor-β 3 is required for secondary palate fusion. Nat Genet 11:409-414
207. Ferguson MW 1988 Palate development. Development 103:41-60
208. Fitzpatrick DR, Denhez F, Kondaiah P, Akhurst RJ 1990 Differ ential expression of TGF β isoforms in murine palatogenesis. Development 109:585-595
209. Pelton RW, Hogan BL, Miller DA, Moses HL 1990 Differential expression of genes encoding TGFs β 1, β 2, and β 3 during murine palate formation. Dev Biol 141:456-460
210. Feijen A, Goumans MJ, van den Eijnden-van Raaij AJ 1994 Expression of activin subunits, activin receptors and follistatin in postimplantation mouse embryos suggests specific developmental ftmctions for different activms. Development 120:3621-3637
211. Roberts VJ, Sawchenko PE, Vale W 1991 Expression of inhibin/activin subunit messenger ribonucleic acids during rat embryo-genesis. Endocrinology 128:3122-3129
212. Taya Y, O'Kane S, Ferguson MW 1999 Pathogenesis of cleft palate in TGF-β3 knockout mice. Development 126:3869-3879
213. Matzuk MM, Kumar TR, Vassalli A, Bickenbach JR, Roop DR, Jaenisch R, Bradley A 1995 Functional analysis of activins in mammalian development. Nature 374:354-356
214. Jones KL 1997 Smith's Recognizable Patterns of Human Malformation, 5th Ed. Philadelphia: W. B. Saunders Company
215. Nakamura T, Takio K, Eto Y, Shibai H, Titani K, Sugino H 1990 Activin-binding protein from rat ovary is follistatin. Science 247: 836-838
216. Matzuk MM, Lu H, Vogel H, Sellheyer K, Roop DR, Bradley A 1995 Multiple defects and perinatally death in mice deficient in follistatin. Nature 372:360-363
217. Guo Q, Kumar TR, Woodruff T, Hadsell LA, DeMayo FJ, Matzuk MM 1998 Overexpression of mouse follistatin causes reproductive defects in transgenic mice. Mol Endocrinol 12:96-106
218. Gamer LW, Wolfman NM, Celeste AJ, Hattersley G, Hewick R, Rosen V 1999 A novel BMP expressed in developing mouse limb, spinal cord, and tail bud is a potent mesoderm inducer in Xenopus embryos. Dev Biol 208:222-232
219. McPherron AC, Lawler AM, Lee SJ 1999 Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11. Nat Genet 22:260-264
220. Nakashima M, Toyono T, Akamine A, Joyner A 1999 Expression of growth/differentiation factor 11, a new member of the BMP/ TGFβ superfamily during mouse embryogenesis. Mech Dev 80: 185-189
221. 1996 Gene Expression in Tooth. Developmental Biology Programme of the University of Helsinki. http://bite-it.helsinki.fi/
222. Jernvall J, Thesleff I 2000 Reiterative signaling and patterning during mammalian tooth morphogenesis. Mech Dev 92:19-29
223. Thesleff I, Sharpe P 1997 Signalling networks regulating dental development. Mech Dev 67:111-123
224. Bei M, Maas R 1998 FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development. Development 125:4325-4333
225. Tucker AS, Matthews KL, Sharpe PT 1998 Transformation of tooth type induced by inhibition of BMP signaling. Science 282:1136-1138
226. Vainio S, Karavanova I, Jowett A, Thesleff I 1993 Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell 75:45-58
227. Peters H, Neubuser A, Balling R 1998 Pax genes and organogenesis: Pax9 meets tooth development. Eur J Oral Sci 106(Suppl 1): 38-43
228. Ferguson CA, Tucker AS, Chfistensen L, Lau AL, Matzuk MM, Sharpe PT 1998 Activin is an essential early mesenchymal signal in tooth development that is required for patterning of murine dentition. Genes Dev 12:2636-2649
229. Matzuk MM 1995 Functional analysis of mammalian members of the transforming growth factor-β superfamily. Trends Endocrinol Metab 6:120-127
230. Kratochwil K, Dull M, Farinas I, Galceran J, Grosschedl R 1996 Lefl expression is activated by BMP-4 and regulares inductive tissue interactions in tooth and hair development. Genes Dev 10: 1382-1394
231. Peters H, Balling R 1999 Teeth. Where and how to make them. Trends Genet 15:59-65
232. Chen Y, Bei M, Woo I, Satokata I, Maas R 1996 Msx1 controls inductive signaling in mammalian tooth morphogenesis. Development 122:3035-3044
233. Aberg T, Wozney J, Thesleff I 1997 Expression patterns of bone morphogenetic proteins (Bmps) in the developing mouse tooth suggest roles in morphogenesis and cell differentiation. Dev Dyn 210:383-396
234. Davis AA, Matzuk MM, Reh TA 2000 Activin A promotes progenitor differentiation into photoreceptors in rodent retina. Mol Cell Neurosci 15:11-21
235. Yoshikawa S, Aota S, Shirayoshi Y, Okazaki K 2000 The ActR-I activin receptor protein is expressed in notochord, lens placode and pituitary primordium cells inthe mouse embryo. Mech Dev 91: 439-444
236. Furuta Y, Hogan BLM 1998 BMP4 is essential for lens induction in the mouse embryo. Genes Dev 12:3764-3775
237. Wawersik S, Purcell P, Rauchman M, Dudley AT, Robertson EJ, Maas R 1999 BMP7 acts in murine lens placode development. Dev Biol 207:176-188
238. Jena N, Martin-Seisdedos C, McCue P, Croce CM 1997 BMP7 null mutation in mice: Developmental defects in skeleton, kidney, and eye. Exp Cell Res 230:28-37
239. Karsenty G, Luo G, Hofmann C, Bradley A 1996 BMP 7 is required for nephrogenesis, eye development, and skeletal patterning. Ann N Y Acad Sci 785:98-107
240. Schrewe H, Gendron-Maguire M, Harbison ML, Gridley T 1994 Mice homozygous for a null mutation of activin βB are viable and fertile. Mech Dev 47:43-51
241. Vassalli A, Matzuk MM, Gardner HAR, Lee K-F, Jaenisch R 1994 Activin/inhibin βB subunit gene disruption leads to defects in eyelid development and female reproduction. Genes Dev 8:414-427
242. Carroll JM, Romero MR, Watt FM 1995 Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis. Cell 83:957-968
243. Luetteke NC, Qiu TH, Peiffer RL, Oliver P, Smithies O, Lee DC 1993 TGF α deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Cell 73:263-278
244. Mann GB, Fowler KJ, Gabriel A, Nice EC, Williams RL, Dunn AR 1993 Mice with a null mutation of the TGF α gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation. Cell 73:249-261
245. Peschon JJ, Slack JL, Reddy P, Stocking KL, Sunnarborg SW, Lee DC, Russell WE, Castner BJ, Johnson RS, Fitzner JN, Boyce RW, Nelson N, Kozlosky CJ, Wolfson MF, Rauch CT, Cerretti DP, Paxton RJ, Match CJ, Black RA 1998 An essential role for ectodomain shedding in mammalian development. Science 282:1281-1284
246. Cohen MM 2001 Problems in the definition of holoprosencephaly. Am J Med Genet 103:183-187
247. Wotton D, Lo RS, Swaby LA, Massague J 1999 Multiple modes of repression by the Smad transcriptional corepressor TGIF. J Biol Chem 274:37105-37110
248. Varlet I, Robertson EJ 1997 Left-right asymmetry in vertebrates. Curr Opin Genet Dev 7:519-523
249. Green EL, Green MC 1942 The development of three manifestations of the short ear gene in the mouse. J Morphol 70:1-19
250. Gruneberg H, Cattanach BM, McLaren A, Wolfe HG, Bowman P 1972 The molars of tabby chimaeras in the mouse. Proc R Soc Lond B Biol Sci 182:183-192
251. Lacombe D, Toutain A, Gorlin RJ, Oley CA, Battin J 1994 Clinical identification of a human equivalent to the short ear (se) murine phenotype. Ann Genet 37:184-191
252. Erlebacher A, Derynck R 1996 Increased expression of TGF-β 2 in osteoblasts results in an osteoporosis-like phenotype. J Cell Biol 132:195-210
253. Gunther T, Doherty M, Karsenty G 2001 Use of transgenic animals in skeleton biology. In: Matzuk MM, Brown CW, Kumar TR, eds. Contemporary Endocrinology: Transgenics in Endocrinology. Totowa, NJ: Humana Press; 385-399
254. 3H10T1/2 cells induces differentiation into distinct mesenchymal cell lineages. DNA Cell Biol 12:871-880
255. Asahina I, Sampath TK, Nishimura I, Hauschka PV 1993 Human osteogenic protein-1 induces both chondroblastic and osteoblastic differentiation of osteoprogenitor cells derived from newborn rat calvaria. J Cell Biol 123:921-933
256. 3H10T1/2, is induced to differentiate into osteoblastic cells by recombinant human bone morphogenetic protein-2. Biochem Biophys Res Commun 172:295-299
257. Wang EA, Rosen V, D'Alessandro JS, Bauduy M, Cordes P, Harada T, Israel DI, Hewick RM, Kems KM, LaPan P, Luxenberg DH, McQuid D, Moutsatsos IK, Nove J, Wozney JM 1990 Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA 87:2220-2224
258. Gruneberg H, Lee AJ 1973 The anatomy and development of brachypodism in the mouse. J Embryol Exp Morphol 30:119-141
259. Landauer W 1952 Brachypodism, a recessive mutation of house mice. J Hered 43:293-298
260. Storm EE, Huynh TV, Copeland NG, Jenkins NA, Kingsley DM, Lee SJ 1994 Limb alterations in brachypodism mice due to mutations in a new member of the TGF β-superfamily. Nature 368:639-643
261. Erlacher L, McCartney J, Piek E, ten Dijke P, Yanagishita M, Oppermann H, Luyten FP 1998 Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis. J Bone Miner Res 13:383-392
262. Hotten GC, Matsumoto T, Kimura M, Bechtold RF, Kron R, Ohara T, Tanaka H, Satoh Y, Okazaki M, Shirai T, Pan H, Kawai S, Pohl JS, Kudo A 1996 Recombinant human growth/differentiation factor 5 stimulates mesenchyme aggregation and chondrogenesis responsible for the skeletal development of limbs. Growth Factors 13:65-74
263. Storm EE, Kingsley DM 1996 Joint patterning defects caused by single and double mutations in members of the bone morphogenetic protein (BMP) family. Development 122:3969-3979
264. Wolfman NM, Hattersley G, Cox K, Celeste AJ, Nelson R, Yamaji N, Dube JL, DiBlasio-Smith E, Nove J, Song JJ, Wozney JM, Rosen V 1997 Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-β gene family. J Clin Invest 100:321-330
265. Storm EE, Kingsley DM 1999 GDF5 coordinates bone and joint formation during digit development. Dev Biol 209:11-27
266. Baur ST, Mai JJ, Dymecki SM 2000 Combinatorial signaling through BMP receptor IB and GDF5: Shaping of the distal mouse limb and the genetics of distal limb diversity. Development 127: 605-619
267. Online Mendelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. MIM no. 113100, 1986. http://www.ncbi. nlm.nih.gov/omim/
268. Online Mendelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. MIM no. 201250, 1986. http://www.ncbi. nlm.nih.gov/omim/
269. Online Mendelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. MIM no. 200700, 1986. http://www.ncbi. nlm.nih.gov/omim/
270. Polinkovsky A, Robin NH, Thomas JT, Irons M, Lynn A, Goodman FR, Reardon W, Kant SG, Brunner HG, van der Burgt I, Chitayat D, McGaughran J, Donnai D, Luyten FP, Warman ML 1997 Mutations in CDMP1 cause autosomal dominant brachydactyly type C. Nat Genet 17:18-19
271. Thomas JT, Lin K, Nandedkar M, Camargo M, Cervenka J, Luyten FP 1996 A human chondrodysplasia due to a mutation in a TGF-β superfamily member. Nat Genet 12:315-317
272. Thomas JT, Kilpatrick MW, Lin K, Erlacher L, Lembessis P, Costa T, Tsipouras P, Luyten FP 1997 Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1. Nat Genet 17:58-64
273. Merino R, Macias D, Ganan Y, Rodriguez-Leon J, Economides AN, Rodriguez-Esteban C, Izpisua-Belmonte JC, Hurle JM 1999 Control of digit formation by activin signalling. Development 126: 2161-2170
274. Katagiri T, Boorla S, Frendo JL, Hogan BL, Karsenty G 1998 Skeletal abnormalities in doubly heterozygous Bmp4 and Bmp7 mice. Dev Genet 22:340-348
275. Green MC 1968 Mechanism of the pleiotropic effects of the short-ear mutant gene in the mouse. J Exp Zool 167:129-150
276. Gamer LW, Cox KA, Small C, Rosen V 2001 Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb. Dev Biol 229:407-420
277. Daluiski A, Engstrand T, Bahamonde ME, Gamer LW, Agius E, Stevenson SL, Cox K, Rosen V, Lyons KM 2001 Bone morphogenetic protein-3 is a negative regulator of bone density. Nat Genet 27:84-88
278. Kinoshita A, Salto T, Tomita H, Makita Y, Yoshida K, Ghadami M, Yamada K, Kondo S, Ikegawa S, Nishimura G, Fukushima Y, Nakagomi T, Saito H, Sugimoto T, Kamegaya M, Hisa K, Murray JC, Taniguchi N, Niikawa N, Yoshiura K 2000 Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease. Nat Genet 26:19-20
279. Ahn K, Mishina Y, Hanks MC, Behringer RR, Crenshaw III EB 2001 BMPR-IA signaling is required for the formation of the apical ectodermal ridge and dorsal-ventral patterning of the limb. Development 128:4449-4461
280. Brunet LJ, McMahon JA, McMahon AP, Harland RM 1998 Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science 280:1455-1457
281. Online Mendelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. MIM no. 185800, 1986. http://www.ncbi. nlm.nih.gov/omim/
282. Online Mendelian Inheritance in Man, OMIM. Johns Hopkins University, Baltimore, MD. MIM no. 186500, 1986. http://www.ncbi. nlm.nih.gov/omim/
283. Gong Y, Krakow D, Marcelino J, Wilkin D, Chitayat D, BabulHirji R, Hudgins L, Cremers CW, Cremers FP, Brunner HG, Reinker K, Rimoin DL, Cohn DH, Goodman FR, Reardon W, Patton M, Francomano CA, Warman ML 1999 Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis. Nat Genet 21:302-304
284. McPherron AC, Lawler AM, Lee SJ 1997 Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member. Nature 387:83-90
285. McPherron AC, Lee SJ 1997 Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci USA 94:12457-12461
286. Lee SJ, McPherron AC 2001 Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA 98:9306-9311
287. Zimmers TA, Davies MV, Koniaris LG, Haynes P, Esquela AF, Tomkinson KN, McPherron AC, Wolfman NM, Lee SJ 2002 Induction of cachexia in mice by systemically administered myostatin. Science 296:1486-1488
288. Brown CW, Houston-Hawkins DE, Woodruff TK, Matzuk MM 2000 Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and reveals new activin functions. Nat Genet 25:453-457
289. Moore MW, Klein RD, Farinas I, Sauer H, Armanini M, Phillips H, Reichardt LF, Ryan AM, Carver-Moore K, Rosenthal A 1996 Renal and neuronal abnormalities in mice lacking GDNF. Nature 382:76 -79
290. Pichel JG, Shen L, Sheng HZ, Granholm AC, Drago J, Grinberg A, Lee EJ, Huang SP, Saarma M, Hoffer BJ, Sariola H, Westphal H 1996 GDNF is required for kidney development and enteric innervation. Cold Spring Harb Symp Quant Biol 61:445-457
291. Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M 1996 Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382:70-73
292. Heuckeroth RO, Enomoto H, Grider JR, Golden JP, Hanke JA, Jackman A, Molliver DC, Bardgett ME, Snider WD, Johnson Jr EM, Milbrandt J 1999 Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons. Neuron 22:253-263
293. Schuchardt A, D'Agati V, Larsson-Blomberg L, Costantini F, Pachnis V 1994 Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367:380-383
294. Cacalano G, Farinas I, Wang LC, Hagler K, Forgie A, Moore M, Armanini M, Phillips H, Ryan AM, Reichardt LF, Hynes M, Davies A, Rosenthal A 1998 GFRα1 is an essential receptor component for GDNF in the developing nervous system and kidney. Neuron 21:53-62
295. Enomoto H, Araki T, Jackman A, Heuckeroth RO, Snider WD, Johnson Jr EM, Milbrandt J 1998 GFR α1-deficient mice have deficits in the enteric nervous system and kidneys. Neuron 21: 317-324
296. Rossi J, Luukko K, Poteryaev D, Laurikainen A, Sun YF, Laakso T, Eerikainen S, Tuominen R, Lakso M, Rauvala H, Arumae U, Pastemack M, Saarma M, Airaksinen MS 1999 Retarded growth and deficits in the enteric and parasympathetic nervous system in mice lacking GFR α2, a functional neurturin receptor. Neuron 22:243-252
297. Takahashi M 2001 The GDNF/RET signaling pathway and human diseases. Cytokine Growth Factor Rev 12:361-373
298. Angrist M, Bolk S, Halushka M, Lapchak PA, Chakravarti A 1996 Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient. Nat Genet 14:341-344
299. Salomon R, Attie T, Pelet A, Bidaud C, Eng C, Amiel J, Sarnacki S, Goulet O, Ricour C, Nihoul-Fekete C, Munnich A, Lyonnet S 1996 Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease. Nat Genet 14:345-347
300. Doray B, Salomon R, Amiel J, Pelet A, Touraine R, Billaud M, Attie T, Bachy B, Munnich A, Lyonnet S 1998 Mutation of the RET ligand, neurturin, supports multigenic inheritance in Hirschsprung disease. Hum Mol Genet 7:1449-1452
301. Zhou B, Bae SK, Malone AC, Levinson BB, Kuo YM, Cilio MR, Bertini E, Hayflick SJ, Gitschier JM 2001 hGFRα-4: A new member of the GDNF receptor family and a candidate for NBIA. Pediatr Neurol 25:156-161
302. Masure S, Cik M, Hoefnagel E, Nosrat CA, Van der Linden I, Scott R, Van Gompel P, Lesage AS, Verhasselt P, Ibanez CF, Gordon RD 2000 Mammalian GFRα-4, a divergent member of the GFRα family of coreceptors for glial cell line-derived neurotrophic factor family ligands, is a receptor for the neurotrophic factor persephin. J Biol Chem 275:39427-39434
303. Tomac AC, Agulnick AD, Haughey N, Chang CF, Zhang Y, Backman C, Morales M, Mattson MP, Wang Y, Westphal H, Hoffer BJ 2002 Effects of cerebral ischemia in mice deficient in persephin. Proc Natl Acad Sci USA 99:9521-9526
304. Honma Y, Araki T, Gianino S, Bruce A, Heuckeroth R, Johnson E, Milbrandt J 2002 Artemin is a vascular-derived neurotropic factor for developing sympathetic neurons. Neuron 35:267-282
305. Robinson GW, Hennighausen L 1997 Inhibins and activins regulate mammary epithelial cell differentiation through mesenchymal-epithelial interactions. Development 124:2701-2708
306. Clark DA, Coker R 1998 Transforming growth factor-β (TGF-β). Int J Biochem Cell Biol 30:293-298
307. King T, Brown NA 1997 Embryonic asymmetry: Left TGFβ at the right time? Curr Biol 7:R212-R215
308. Letterio JJ, Bottinger EP 1998 TGF-β knockout and dominant-negative receptor transgenic mice. Miner Electrolyte Metab 24:161-167
309. Moses HL, Serra R 1996 Regulation of differentiation by TGF-β. Curr Opin Genet Dev 6:581-586
310. Wall NA, Hogan BL 1994 TGF-β related genes in development. Curr Opin Genet Dev 4:517-522
311. Whitworth DJ, Behringer RR 2001 The transgenic mouse in studies of mammalian sexual differentiation. In: Matzuk MM, Brown CW, Kumar TR, eds. Contemporary Endocrinology: Transgenics in Endocrinology. Totowa, NJ: Humana Press; 19-39
312. Mishina Y 2001 The in vivo function of Mullerian-inhibiting substance during mammalian sexual development. In: Matzuk MM, Brown CW, Kumar TR, eds. Contemporary Endocrinology: Transgenics in Endocrinology. Totowa, NJ: Humana Press; 41-59
313. Teixeira J, Maheswaran S, Donahoe PK 2001 Mullerian inhibiting substance: An instructive developmental hormone with diagnostic and possible therapeutic applications. Endocr Rev 22:657-674
314. Behringer RR 1994 The in vivo roles of Mullerian-inhibiting substance. Curr Top Dev Biol 29:171-187
315. Behringer RR, Finegold MJ, Cate RL 1994 Müllerian-inhibiting substance function during mammalian sexual development. Cell 79:415-425
316. Rouiller-Fabre V, Carmona S, Merhi RA, Cate R, Habert R, Vigier B 1998 Effect of anti-Mullerian hormone on Sertoli and Leydig cell functions in fetal and immature rats. Endocrinology 139:1213-1220
317. Sriraman V, Niu E, Matias JR, Donahoe PK, MacLaughlin DT, Hardy MP, Lee MM 2001 Mullerian inhibiting substance inhibits testosterone synthesis in adult rats. J Androl 22:750-758
318. Behringer RR 1995 The Mullerian inhibitor and mammalian sexual development. Philos Trans R Soc Lond B Biol Sci 350:285-288; discussion 289
319. Behringer RR, Cate RL, Froelick GJ, Palmiter RD, Brinster RL 1990 Abnormal sexual development in transgenic mice chronically expressing Müllerian-inhibiting substance. Nature 345:167-170
320. Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JT, Grootegoed JA, Themmen AP 1999 Control of primordial follicle recruitment by anti-Mullerian hormone in the mouse ovary. Endocrinology 140:5789-5796
321. Durlinger AL, Gruijters MJ, Kramer P, Karels B, Kumar TR, Matzuk MM, Rose UM, de Jong FH, Uilenbroek JT, Grootegoed JA, Themmen AP 2001 Anti-Mullerian hormone attenuates the effects of FSH on follicle development in the mouse ovary. Endocrinology 142:4891-4899
322. Mishina Y, Rey R, Finegold MJ, Matzuk MM, Josso N, Cate RL, Behringer RR 1996 Genetic analysis of the Mullerian-inhibiting substance signal transduction pathway in mammalian sexual differentiation. Genes Dev 10:2577-2587
323. Mishina Y, Whitworth DJ, Racine C, Behringer RR 1999 High specificity of Mullerian-inhibiting substance signaling in vivo. Endocrinology 140:2084-2088
324. Meyers-Wallen VN 1993 Genetics of sexual differentiation and anomalies in dogs and cats. J Reprod Fertil Suppl 47:441-452
325. Belville C, Josso N, Picard JY 1999 Persistence of Mullerian derivatives in males. Am J Med Genet 89:218-223
326. Visser JA, Olaso R, Verhoef-Post M, Kramer P, Themmen AP, Ingraham HA 2001 The serine/threonine transmembrane receptor ALK2 mediates Mullerian inhibiting substance signaling. Mol Endocrinol 15:936-945
327. Clarke TR, Hoshiya Y, Yi SE, Liu X, Lyons KM, Donahoe PK 2001 Mullerian inhibiting substance signaling uses a bone morphogenetic protein (BMP)-like pathway mediated by ALK2 and induces SMAD6 expression. Mol Endocrinol 15:946-959
328. Jamin SP, Arango NA, Mishina Y, Hanks MC, Behringer RR 2002 Requirement of Bmpr1a for Mullerian duct regression during male sexual development. Nat Genet 32:408-410
329. Giuili G, Shen WH, Ingraham HA 1997 The nuclear receptor SF-1 mediates sexually dimorphic expression of Mullerian inhibiting substance, in vivo. Development 124:1799-807
330. Arango NA, Lovell-Badge R, Behringer RR 1999 Targeted mutagenesis of the endogenous mouse Mis gene promoter: In vivo definition of genetic pathways of vertebrate sexual development. Cell 99:409-419
331. De Felici M, Dolci S, Pesce M 1992 Cellular and molecular aspects of mouse primordial germ cell migration and proliferation in culture. Int J Dev Biol 36:205-213
332. Ginsburg M, Snow MH, McLaren A 1990 Primordial germ cells in the mouse embryo during gastrulation. Development 110:521-528
333. Lawson KA, Hage WJ 1994 Clonal analysis of the origin of primordial germ cells in the mouse. Ciba Found Symp 182:68-91
334. Anderson R, Copeland TK, Scholer H, Heasman J, Wylie C 2000 The onset of germ cell migration in the mouse embryo. Mech Dev 91:61-68
335. Gomperts M, Wylie C, Heasman J 1994 Primordial germ cell migration. Ciba Found Symp 182:121-134; discussion 134-139
336. Tam PP, Snow MH 1981 Proliferation and migration of primordial germ cells during compensatory growth in mouse embryos. J Embryol Exp Morphol 64:133-147
337. Zhao GQ, Garbers DL 2002 Male germ cell specification and differentiation. Dev Cell 2:537-547
338. Lawson KA, Dunn NR, Roelen BA, Zeinstra LM, Davis AM, Wright CV, Korving JP, Hogan BL 1999 Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 13:424-436
339. Coucouvanis E, Martin GR 1999 BMP signaling plays a role in visceral endoderm differentiation and cavitation in the early mouse embryo. Development 126:535-546
340. Chang H, Matzuk MM 2001 Smad5 is required for mouse primordial germ cell development. Mech Dev 104:61-67
341. Richards AJ, Enders GC, Resnick JL 1999 Activin and TGFβ limit murine primordial germ cell proliferation. Dev Biol 207:470-475
342. Kumar TR, Wang Y, Lu N, Matzuk MM 1997 Follicle stimulating hormone is required for ovarian follicle maturation bur not male fertility. Nar Genet 15:201-204
343. Ying SY 1987 Inhibins and activins: Chemical properties and biological activity. Proc Soc Exp Biol Med 186:253-264
344. Kumar TR, Varani S, Wreford NG, Telfer NM, de Kretser DM, Matzuk MM 2001 Male reproductive phenotypes m double mutant mice lacking both FSHβ and activin receptor IIA. Endocrinology 142:3512-3518
345. Matzuk MM, Finegold MJ, Su J-GJ, Hsueh AJW, Bradley A 1992 α-Inhibin is a tumor-suppressor gene with gonadal specificity in mice. Nature 360:313-319
346. Matzuk MM, Finegold MJ, Mather JP, Krummen L, Lu H, Bradley A 1994 Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice. Proc Natl Acad Sci USA 91:8817-8821
347. Coerver KA, Woodruff TK, Finegold MJ, Mather J, Bradley A, Matzuk MM 1996 Activin signaling through activin receptor type II causes the cachexia-like symptoms in inhibin-deficient mice. Mol Endocrinol 10:534-543
348. Li Q, Karam SM, Coerver KA, Matzuk MM, Gordon JI 1998 Stimulation of activin receptor II signaling pathways inhibits differentiation of multiple gastric epithelial lineages. Mol Endocrinol 12:181-192
349. Cipriano S, Chen L, Bums K, Koff A, Matzuk M 2001 Inhibin and p27 interact to regulate gonadal tumorigenesis. Mol Endocrinol 15:985-996
350. Pierson TM, Wang Y, DeMayo FJ, Matzuk MM, Tsai SY, O'Malley BW 2000 Regulable expression of inhibin A in wild-type and inhibin α null mice. Mol Endocrinol 14:1075-1085
351. Shelling AN, Burton KA, Chand AL, van Ee CC, France JT, Farquhar CM, Milsom SR, Love DR, Gersak K, Aittomaki K, Winship IM 2000 Inhibin: A candidate gene for premature ovarian failure. Hum Reprod 15:2644-2649
352. Matzuk MM, Finegold MJ, Mishina Y, Bradley A, Behringer RR 1995 Synergistic effects of inhibins and Mullerian-inhibiting substance on testicular tumorigenesis. Mol Endocrinol 9:1337-1345
353. Zhao G-Q, Deng K, Labosky PA, Liaw L, Hogan BLM 1996 The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse. Genes Dev 10:1657-1669
354. Zhao G-Q, Liaw L, Hogan BLM 1998 Bone morphogenetic protein 8A plays a role in the maintenance of spermatogenesis and the integrity of the epididymis. Development 125:1103-1112
355. Zhao GQ, Hogan BL 1996 Evidence that mouse Bmp8a (Op2) and Bmp8b are duplicated genes that play a role in spermatogenesis and placental development. Mech Dev 57:159-168
356. Elvin JA, Yan C, Matzuk MM 2000 Oocyte-expressed TGF-β superfamily members in female fertility. Mol Cell Endocrinol 159:1-5
357. Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM 1996 Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383:531-535
358. Carabatsos MJ, Elvin JA, Matzuk MM, Albertini DF 1998 Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice. Dev Biol 204:373-384
359. Elvin JA, Yan C, Wang P, Nishimori K, Matzuk MM 1999 Molecular characterization of the follicle defects in the growth differentiation factor-9-deficient ovary. Mol Endocrinol 13:1018-1034
360. Latham KE, Bautista FD, Hirao Y, O'Brien MJ, Eppig JJ 1999 Comparison of protein synthesis patterns in mouse cumulus cells and murai granulosa cells: Effects of follide-stimulating hormone and insulin on granulosa cell differentiation in vitro. Biol Reprod 61:482-492
361. Eppig JJ, Chesnel F, Hirao Y, O'Brien MJ, Pendola FL, Watanabe S, Wigglesworth K 1997 Oocyte control of granulosa cell deveiopment: How and why. Hum Reprod 12:127-132
362. Elvin JA, Clark AT, Wang P, Wolfman NM, Matzuk MM 1999 Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Mol Endocrinol 13:1035-1048
363. Elvin JA, Yan C, Matzuk MM 2000 Growth differentiation factor-9 stimulates progesterone synthesis in granulosa cells via a prostaglandin E2/EP2 receptor pathway. Proc Natl Acad Sci USA 97: 10288-10293
364. Yan C, Wang P, DeMayo J, DeMayo F, Elvin J, Carino C, Prasad S, Skinner S, Dunbar B, Dube J, Celeste A, Matzuk M 2001 Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 15: 854-866
365. Galloway SM, McNatty KP, Cambridge LM, Laitinen MP, Juengel JL, Jokiranta TS, McLaren RJ, Luiro K, Dodds KG, Montgomery GW, Beattie AE, Davis GH, Ritvos O 2000 Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet 25:279-283
366. Varani S, Elvin JA, Yan C, DeMayo J, DeMayo FJ, Horton HF, Byrne MC, Matzuk MM 2002 Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol 16:1154-1167
367. Breviario F, d'Aniello EM, Golay J, Peri G, Bottazzi B, Bairoch A, Saccone S, Marzella R, Predazzi V, Rocchi M 1992 Interleukin1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component. J Biol Chem 267:22190 -22197
368. Yi SE, LaPolt PS, Yoon BS, Chen JY, Lu JK, Lyons KM 2001 The type I BMP receptor BmprIB is essential for female reproductive function. Proc Natl Acad Sci USA 98:7994-7999
369. Wilson T, Wu XY, Juengel JL, Ross IK, Lumsden JM, Lord EA, Dodds KG, Walling GA, McEwan JC, O'Connell AR, McNatty KP, Montgomery GW 2001 Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol Reprod 64:1225-1235
370. Dyson S, Gurdon JB 1998 The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors. Cell 93:557-568
371. Ferguson EL, Anderson KV 1992 Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo. Cell 71:451-461
372. Lecuit T, Brook WJ, Ng M, Calleja M, Sun H, Cohen SM 1996 Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing. Nature 381:387-393
373. Agius E, Oelgeschlager M, Wessely O, Kemp C, De Robertis EM 2000 Endodermal Nodal-related signals and mesoderm induction in Xenopus. Development 127:1173-1183
374. Blobe GC, Schiemann WP, Lodish HF 2000 Role of transforming growth factor β in human disease. N Engl J Med 342:1350-1358
375. Berg JN, Gallione CJ, Stenzel TT, Johnson DW, Allen WP, Schwartz CE, Jackson CE, Porteous ME, Marchuk DA 1997 The activin receptor-like kinase 1 gene: Genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Am J Hum Genet 61:60-67
376. D'Abronzo FH, Swearingen B, Klibanski A, Alexander JM 1999 Mutational analysis of activin/transforming growth factor-β type I and type II receptor kinases in human pituitary tumors. J Clin Endocrinol Metab 84:1716-1721
377. Loscalzo J 2001 Genetic clues to the cause of primary pulmonary hypertension. N Engl J Med 345:367-371
378. Howe JR, Bair JL, Sayed MG, Anderson ME, Mitros FA, Petersen GM, Velculescu VE, Traverso G, Vogelstein B 2001 Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet 28:184-187
379. Miller RW, Rubinstein JH 1995 Tumors in Rubinstein-Taybi syndrome. Am J Med Genet 56:112-115
380. Shovlin CL, Hughes JM, Scott J, Seidman CE, Seidman JG 1997 Characterization of endoglin and identification of novel mutations in hereditary hemorrhagic telangiectasia. Am J Hum Genet 61:68-79
381. Riggins GJ, Kinzler KW, Vogelstein B, Thiagalingam S 1997 Frequency of Smad gene mutations in human cancers. Nature 388:28-29
382. Uchida K, Nagatake M, Osada H, Yatabe Y, Kondo M, Mitsudomi T, Masuda A, Takahashi T 1996 Somatic in vivo alterations of the JV18-1 gene at 18q21 in human lung cancers. Cell 87:1215-1224
383. Thiagalingam S, Lengauer C, Leach FS, Schutte M, Hahn SA, Overhauser J, Willson JK, Markowitz S, Hamilton SR, Kern SE, Kinzler KW, Vogelstein B 1996 Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nat Genet 13:343-346
384. Howe JR, Roth S, Ringold JC, Summers RW, Jarvinen HJ, Sistonen P, Tomlinson IP, Houlston RS, Bevan S, Mitros FA, Stone EM, Aaltonen LA 1998 Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 280:1036-1037
385. Kinoshita A, Saito T, Tomita H, Makita Y, Yoshida K, Ghadami M, Yamada K, Kondo S, Ikegawa S, Nishimura G, Fukushima Y, Nakagomi T, Saito H, Sugimoto T, Kamegaya M, Hisa K, Murray JC, Taniguchi N, Niikawa N, Yoshiura K 2000 Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease. Nat Genet 26:19-20
386. Maehara Y, Kakeji Y, Kabashima A, Emi Y, Watanabe A, Akazawa K, Baba H, Kohnoe S, Sugimachi K 1999 Role of transforming growth factor-β 1 in invasion and metastasis in gastric carcinoma. J Clin Oncol 17:607-614
387. Yamada Y, Miyauchi A, Goto J, Takagi Y, Okuizumi H, Kanematsu M, Hase M, Takai H, Harada A, Ikeda K 1998 Association of a polymorphism of the transforming growth factor-β1 gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women. J Bone Miner Res 13:1569-1576
388. Border WA, Noble NA 1994 Transforming growth factor β in tissue fibrosis. N Engl J Med 331:1286-1292
389. Li B, Khanna A, Sharma V, Singh T, Suthanthiran M, August P 1999 TGF-β1 DNA polymorphisms, protein levels, and blood pressure. Hypertension 33:271-275
390. Chen T, Carter D, Garrigue-Antar L, Reiss M 1998 Transforming growth factor β type I receptor kinase mutant associated with metastatic breast cancer. Cancer Res 58:4805-4810
391. Chen T, Yan W, Wells RG, Rimm DL, McNiff J, Leffell D, Reiss M 2001 Novel inactivating mutations of transforming growth factor-β type I receptor gene in head-and-neck cancer metastases. Int J Cancer 93:653-661
392. Grady WM, Myeroff LL, Swinler SE, Rajput A, Thiagalingam S, Lutterbaugh JD, Neumann A, Brattain MG, Chang J, Kim SJ, Kinzler KW, Vogelstein B, Willson JK, Markowitz S 1999 Mutational inactivation of transforming growth factor β receptor type II in microsatellite stable colon cancers. Cancer Res 59:320-324
393. Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW, Vogelstein B, Brattain M, Willson JKV 1995 Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science 268:1336-1338
394. Myeroff LL, Parsons R, Kim SJ, Hedrick L, Cho KR, Orth K, Mathis M, Kinzler KW, Lutterbaugh J, Park K 1995 A transforming growth factor β receptor type II gene mutation common in colon and gastric but rare in endometrial cancers with microsatellite instability. Cancer Res 55:5545-5547
395. Knaus PI, Lindemann D, DeCoteau JF, Perlman R, Yankelev H, Hille M, Kadin ME, Lodish HF 1996 A dominant inhibitory mutant of the type II transforming growth factor β receptor in the malignant progression of a cutaneous T-cell lymphoma. Mol Cell Biol 16:3480-3489
396. Sun L, Wu G, Willson JK, Zborowska E, Yang J, Rajkarunanayake I, Wang J, Gentry LE, Wang XF, Brattain MG 1994 Expression of transforming growth factor β type II receptor leads to reduced malignancy in human breast cancer MCF-7 cells. J Biol Chem 269:26449-26455
397. McCaffrey TA, Du B, Consigli S, Szabo P, Bray PJ, Hartner L, Weksler BB, Sanborn TA, Bergman G, Bush Jr HL 1997 Genomic instability in the type II TGF-β1 receptor gene in atherosclerotic and restenotic vascular cells. J Clin Invest 100:2182-2188
398. Lau AL, Kumar TR, Nishimori K, Bonadio J, Matzuk MM 2000 Activin βC and activin βE genes are not essential for mouse liver growth, differentiation, and regeneration. Mol Cell Biol 20:6127-6137
399. Winnier G, Blessing M, Labosky PA, Hogan BL 1995 Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9:2105-2116
400. Dunn NR, Winnier GE, Hargett LK, Schrick JJ, Fogo AB, Hogan BL 1997 Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol 188:235-247
401. King JA, Marker PC, Seung KJ, Kingsley DM 1994 BMP5 and the molecular, skeletal, and soft-tissue alterations in short ear mice. Dev Biol 166:112-122
402. Settle S, Marker P, Gurley K, Sinha A, Thacker A, Wang Y, Higgins K, Cunha G, Kingsley DM 2001 The bmp family member gdf7 is required for seminal vesicle growth, branching morphogenesis, and cytodifferentiation. Dev Biol 234:138-150
403. Zhao R, Lawler AM, Lee SJ 1999 Characterization of GDF-10 expression patterns and null mice. Dev Biol 212:68-79
404. Hsiao EC, Koniaris LG, Zimmers-Koniaris T, Sebald SM, Huynh TV, Lee SJ 2000 Characterization of growth-differentiation factor 15, a transforming growth factor β superfamily member induced following liver injury. Mol Cell Biol 20:3742-3751
405. Deleted in proof
406. Collignon J, Varlet I, Robertson EJ 1996 Relationship between asymmetric nodal expression and the direction of embryonic turning. Nature 381:155-158
407. Brennan J, Lu CC, Norris DP, Rodriguez TA, Beddington RS, Robertson EJ 2001 Nodal signalling in the epiblast patterns the early mouse embryo. Nature 411:965-969
408. Gu Z, Nomura M, Simpson BB, Lei H, Feijen A, van den Eijnden-van Raaij J, Donahoe PK, Li E 1998 The type I activin receptor ActRIIB is required for egg cylinder organization and gastrulation in the mouse. Genes Dev 12:844-857
409. Yi SE, Daluiski A, Pederson R, Rosen V, Lyons KM 2000 The type I BMP receptor BMPRIB is required for chondrogenesis in the mouse limb. Development 127:621-630
410. Matzuk MM, Kumar TR, Shou W, Coerver KA, Lau AL, Behringer RR, Finegold MJ 1996 Transgenic models to study the roles of inhibins and activins in reproduction, oncogenesis, and development. Recent Prog Horm Res 51:123-157
411. Xu T, Bianco P, Fisher LW, Longenecker G, Smith E, Goldstein S, Bonadio J, Boskey A, Heegaard AM, Sommer B, Satomura K, Dominguez P, Zhao C, Kulkarni AB, Robey PG, Young MF 1998 Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nat Genet 20:78-82
412. Constam DB, Robertson EJ 2000 SPC4/PACE4 regulates a TGFβ signaling network during axis formation. Genes Dev 14:1146-1155
413. Roebroek AJ, Umans L, Pauli IG, Robertson EJ, van Leuven F, Van de Ven WJ, Constam DB 1998 Failure of ventral closure and axial rotation in embryos lacking the proprotein convertase Furin. Development 125:4863-4876
414. Lawler J, Sunday M, Thibert V, Duquette M, George EL, Rayburn H, Hynes RO 1998 Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. J Clin Invest 101:982-992
415. Waldrip WR, Bikoff EK, Hoodless PA, Wrana JL, Robertson EJ 1998 Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo. Cell 92:797-808
416. Weinstein M, Yang X, Li C, Xu X, Gotay J, Deng CX 1998 Failure of egg cylinder elongation and mesoderm induction in mouse embryos lacking the tumor suppressor smad2. Proc Natl Acad Sci USA 95:9378-9383
417. Zhu Y, Richardson JA, Parada LF, Graff JM 1998 Smad3 mutant mice develop metastatic colorectal cancer. Cell 94:703-714
418. Yang X, Letterio JJ, Lechleider RJ, Chen L, Hayman R, Gu H, Roberts AB, Deng C 1999 Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-β. EMBO J 18:1280-1291
419. Datto MB, Frederick JP, Pan L, Borton AJ, Zhuang Y, Wang XF 1999 Targeted disruption of Smad3 reveals an essential role in transforming growth factor β-mediated signal transduction. Mol Cell Biol 19:2495-2504
420. Ashcroft GS, Yang X, Glick AB, Weinstein M, Letterio JL, Mizel DE, Anzano M, Greenwell-Wild T, Wahl SM, Deng C, Roberts AB 1999 Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol 1:260-266
421. Sirard C, de la Pompa JL, Elia A, Itie A, Mirtsos C, Cheung A, Hahn S, Wakeham A, Schwartz L, Kern SE, Rossant J, Mak TW 1998 The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev 12:107-119
422. Yang X, Li C, Xu X, Deng C 1998 The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice. Proc Natl Acad Sci USA 95:3667-3672
423. Oike Y, Takakura N, Hata A, Kaname T, Akizuki M, Yamaguchi Y, Yasue H, Araki K, Yamamura K, Suda T 1999 Mice homozygous for a truncated form of CREB-binding protein exhibit defects in hematopoiesis and vasculo-angiogenesis. Blood 93:2771-2779
424. Brown DJ, Kim TB, Petty EM, Downs CA, Martin DM, Strouse PJ, Moroi SE, Milunsky JM, Lesperance MM 2002 Autosomal dominant stapes ankylosis with broad thumbs and toes, hyperopia, and skeletal anomalies is caused by heterozygous nonsense and frameshift mutations in NOG, the gene encoding noggin. Am J Hum Genet 71:618-624