Regulation of BMP/Dpp signaling during embryonic development

Cellular and Molecular Life Sciences

Volumn 57, Issue 6, 2000, Pages 943-956

  Nakayama, T ^a   Cui, Y ^a   Christian, J L ^a  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

Bone morphologic protein (BMP); Decapentaplegic (Dpp); Embryo; Signal transduction; Smad

Indexed keywords

BONE MORPHOGENETIC PROTEIN 4; BONE MORPHOGENETIC PROTEIN RECEPTOR; DECAPENTAPLEGIC; MORPHOGEN; SMAD PROTEIN; UNCLASSIFIED DRUG;

BONE DEVELOPMENT; EMBRYO DEVELOPMENT; NONHUMAN; PROTEIN BINDING; REVIEW; SIGNAL TRANSDUCTION;

HEXAPODA;

EID: 0033942449     PISSN: 1420682X     EISSN: None     Source Type: Journal    
DOI: 10.1007/PL00000736     Document Type: Review

References (150)

1. 1 Wozney J. M., Rosen V., Celeste A. J., Mitsock L. M., Whitters M. J., Kriz R. W. et al. (1988) Novel regulators of hone formation: molecular clones and activities. Science 242: 1528-1534
2. 2 Hogan B. L. M. (1996) Bone morphogenetic proteins: multi-functional regulators of vertebrate development. Genes Dev. 10: 1580-1594
3. 3 Zhang H. and Bradley A. (1996) Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development 122: 2977-2986
4. 4 Winnier G., Blessing M., Labosky P. A. and Hogan B. L. M. (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev. 9: 2105-2116
5. 5 Furuta Y. and Hogan B. L. M. (1998) BMP4 is essential for lens induction in the mouse embryo. Genes Dev. 12: 3764-3775
6. 6 Lawson K. A., Dunn N. R., Roelen B. A. J., Zeinstra L. M., Davis A. M., Wright C. V. E. et al. (1999) Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 13: 424-436
7. 7 Dunn N. R., Winnier G. E., Hargett L. K., Schrick J. J., Fogo A. B. and Hogan B. L. M. (1997) Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev. Biol. 188: 235-247
8. 8 Clement J. H., Fettes P., Knochel S., Lef J. and Knochel W. (1995) Bone morphogenetic protein 2 in the early development of Xenopus laevis. Mech. Dev. 52: 357-370
9. 9 Dale L., Howes G., Price B. M. J. and Smith J. C. (1992) Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. Development 115: 573-585
10. 10 Jones C. M., Lyons K. M., Lapan P. M., Wright C. V. and Hogan B. L. M. (1992) DVR-4 (Bone Morphogenetic Protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction. Development 115: 639-647
11. 11 Fainsod A., Steinbeisser H. and De Robertis E. M. (1994) On the function of BMP-4 in patterning the marginal zone of the Xenopus embryo. EMBO J. 13: 5015-5025
12. 12 Wilson P. A. and Hemmati-Brivanlou A. (1995) Induction of epidermis and inhibition of neural fate by Bmp-4. Nature 376: 331-333
13. 13 Graff J. M., Thies R. S., Song J. J., Celeste A. J. and Melton D. A. (1994) Studies with a Xenopus, BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo. Cell 79: 169-179
14. 14 Suzuki A., Thies R. S., Yamaji N., Song J. J., Wozney J. M., Murakami K. et al. (1994) A truncated bone morphogenetic protein receptor affects dorsal-ventral patterning in the early Xenopus embryo. Proc. Natl. Acad. Sci. USA 91: 10255-10259
15. 15 Maéno M., Ong R. C., Suzuki A., Ueno N. and Kung H.-F. (1994) A truncated bone morphogenetic protein 4 receptor alters the fate of ventral mesoderm to dorsal mesoderm: roles of animal pole tissue in the development of ventral mesoderm. Proc. Natl. Acad. Sci. USA 91: 10260-10264
16. 16 Hawley S. H. B., Wünnenberg-Stapleton K., Hashimoto C., Laurent M. N., Watabe T., Blumberg B. W. et al. (1995) Disruption of BMP signals in embryonic Xenopus ectoderm leads to direct neural induction. Genes Dev. 9: 2923-2935
17. 17 Suzuki A., Kaneko E., Ueno N. and Hemmati-Brivanlou A. (1997) Regulation of epidermal induction by BMP2 and BMP7 signaling. Dev. Biol. 189: 112-122
18. 18 Frisch A. and Wright C. V. E. (1998) XBMPRII, a novel Xenopus type II receptor mediating BMP signaling in embryonic tissues. Development 125: 431-442
19. 19 Dale L. and Jones C. M. (1999) BMP signalling in early Xenopus development. Bioessays 21: 751-760
20. 20 Kishimoto Y., Lee K.-H., Zon L., Hammerschmidt M. and Schulte-Merker S. (1997) The molecular nature of zebrafish swirl: BMP2 function is essential during early dorsoventral patterning. Development 124: 4457-4466
21. 21 Padgett R. W., St. Johnston R. D. and Gelbart W. M. (1987) A transcript from a Drosophila pattern gene predicts a protein homologous to the transforming growth factor-β family. Nature 325: 81-84
22. 22 Ferguson E. L. (1996) Conservation of dorsal-ventral patterning in arthropods and chordates. Curr. Opin. Genet. Dev. 6: 424-431
23. 23 Hogan B. L. M. (1996) Bone morphogenetic proteins in development. Curr. Opin. Genet. Dev. 6: 432-438
24. 24 Mehler M. F., Mabie P. C., Zhang D. and Kessler J. A. (1997) Bone morphogenetic proteins in the nervous system. Trends Neurosci. 20: 309-317
25. 25 Dale L. and Wardle F. C. (1999) A gradient of BMP activity specifies dorsal-ventral fates in early Xenopus embryos. Semin. Cell Dev. Biol. 10: 319-326
26. 26 Podos S. D. and Ferguson E. L. (1999) Morphogen gradients: new insights from DPP. Trends Genet. 15: 396-402
27. 27 Yamashita H., ten Dijke P., Heldin C. H. and Miyazono K. (1996) Bone morphogenetic protein receptors. Bone 19: 569-574
28. 28 Massagué J. (1998) TGF-β signal transduction. Annu. Rev. Biochem. 67: 753-791
29. 29 Haerry T. E., Khalsa O., O'Connor M. B. and Wharton K. A. (1998) Synergistic signaling by two BMP ligands through the SAX and TKV receptors controls wing growth and patterning in Drosophila. Development 125: 3977-3987
30. 30 Neul J. L. and Ferguson E. L. (1998) Spatially restricted activation of the SAX receptor by SCW modulates DPP/ TKV signaling in Drosophila dorsal-ventral patterning. Cell 95: 483-494
31. 31 Nguyen M., Park S., Marqués G. and Arora K. (1998) Interpretation of a BMP activity gradient in Drosophila embryos depends on synergistic signaling by two type I receptors, SAX and TKV. Cell 95: 495-506
32. 32 Attisano L. and Wrana J. L. (1998) Mads and Smads in TGFβ signalling. Curr. Opin. Cell Biol. 10: 188-194
33. 33 Kretzschmar M. and Massagué J. (1998) SMADs: mediators and regulators of TGF-β signaling. Curr. Opin. Genet. Dev. 8: 103-111
34. 34 Whitman M. (1998) Smads and early developmental signaling by the TGFβ superfamily. Genes Dev. 12: 2445-2462
35. 35 Kawabata M. and Miyazono K. (1999) Signal transduction of the TGF-β superfamily by Smad proteins. J. Biochem. 125: 9-16
36. 36 Christian J. L. and Nakayama T. (1999) Can't get no SMADisfaction: Smad proteins as positive and negative regulators of TGF-β family signals. Bioessays 21: 382-390
37. 37 Zhang Y. and Derynck R. (1999) Regulation of Smad signalling by protein associations and signalling crosstalk. Trends Cell Biol. 9: 274-279
38. 38 Piek E., Heldin C.-H. and ten Dijke P. (1999) Specificity, diversity, and regulation in TGF-β superfamily signaling. FASEB J. 13: 2105-2124
39. 39 Yang X., Castilla L. H., Xu X., Li C., Gotay J., Weinstein M. et al. (1999) Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development 126: 1571-1580
40. 40 Chang H., Huylebroeck D., Verschueren K., Guo Q., Malzuk M. M. and Zwijsen A. (1999) Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development 126: 1631-1642
41. 41 Müller F., Blader P., Rastegar S., Fischer N., Knöchel W. and Strähle U. (1999) Characterization of zebrafish smad1, smad2 and smad5: the amino-terminus of Smad1 and Smad5 is required for specific function in the embryo. Mech. Dev. 88: 73-88
42. 42 Dick A., Meier A. and Hammerschmidt M. (1999) Smad1 and Smad5 have distinct roles during dorsoventral patterning of the zebrafish embryo. Dev. Dyn. 216: 285-298
43. 43 Hild M., Dick A., Rauch G.-J., Meier A., Bouwmeester T., Haffter P. et al. (1999) The smad5 mutation somitabun blocks Bmp2b signaling during early dorsoventral patterning of the zebrafish embryo. Development 126: 2149-2159
44. 44 Meersseman G., Verschueren K., Nelles L., Blumenstock C., Kraft H., Wuytens G. et al. (1997) The C-terminal domain of Mad-like signal transducers is sufficient for biological activity in the Xenopus embryo and transcriptional activation. Mech. Dev. 61: 127-140
45. 45 Watanabe T. K., Suzuki M., Omori Y., Hishigaki H., Horie M., Kanemoto N. et al. (1997) Cloning and characterization of a novel member of the human Mad gene family (MADH6). Genomics 42: 446-451
46. 46 Zhao G.-Q. and Hogan B. L. M. (1997) Evidence that Mothers-against-dpp-related 1 (Madr 1) plays a role in the initiation and maintenance of spermatogenesis in the mouse. Mech. Dev. 61: 63-73
47. 47 Dick A., Risau W. and Drexler H. (1998) Expression of Smad1 and Smad2 during embryogenesis suggests a role in organ development. Dev. Dyn. 211: 293-305
48. 48 Nishita M., Ueno N. and Shibuya H. (1999) Smad8B, a Smad8 splice variant lacking the SSXS site that inhibits Smad8-mediated signalling. Genes Cells 4: 583-591
49. 49 LeSueur J. A. and Graff J. M. (1999) Spemann organizer activity of Smad10. Development 126: 137-146
50. 50 Masuyama N., Hanafusa H., Kusakabe M., Shibuya H. and Nishida E. (1999) Identification of two Smad4 proteins in Xenopus. Their common and distinct properties. J. Biol. Chem. 274: 12163-12170
51. 51 Howell M., Itoh F., Pierreux C. E., Valgeirsdottir S., Itoh S., ten Dijke P. et al. (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
52. 52 Wotton D., Lo R. S., Lee S. and Massagué J. (1999) A Smad transcriptional corepressor. Cell 97: 29-39
53. 53 Luo K., Stroschein S. L., Wang W., Chen D., Martens E., Zhou S. et al. (1999) The Ski oncoprotein interacts with the Smad proteins to repress TGFβ signaling. Genes Dev. 13: 2196-2206
54. 54 Sun Y., Liu X., Eaton E. N., Lane W. S., Lodish H. F. and Weinberg R. A. (1999) Interaction of the Ski oncoprotein with Smad3 regulates TGF-β signaling. Mol. Cell 4: 499-509
55. 55 Akiyoshi S., Inoue H., Hanai J., Kusanagi K., Nemoto N., Miyazono K. et al. (1999) c-Ski acts as a transcriptional co-repressor in transforming growth factor-β signaling through interaction with Smads. J. Biol. Chem. 274: 35269-35277
56. 56 Kim J., Johnson K., Chen H. J., Carroll S. and Laughon A. (1997) Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Nature 388: 304-308
57. 57 Waltzer L. and Bienz M. (1999) A function of CBP as a transcriptional co-activator during Dpp signalling. EMBO J. 18: 1630-1641
58. 58 Xu X., Yin Z., Hudson J. B., Ferguson E. L. and Frasch M. (1998) Smad proteins act in combination with synergistic and antagonistic regulators to target Dpp responses to the Drosophila mesoderm. Genes Dev. 12: 2354-2370
59. 59 Hata A., Seoane J., Lagna G., Montalvo E., Hemmati-Brivanlou A. and Massagué J. (2000) OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways. Cell 100: 229-240
60. 60 Cui Y., Jean F., Thomas G. and Christian J. L. (1998) BMP-4 is proteolytically activated by furin and or PC6 during vertebrate embryonic development. EMBO J. 17: 4735-4743
61. 61 Constam D. B. and Robertson E. J. (1999) Regulation of bone morphogenetic protein activity by pro domains and proprotein convertases. J. Cell Biol. 144: 139-149
62. 62 Aono A., Hazama M., Notoya K., Taketomi S., Yamasaki H., Tsukuda R. et al. (1995) Potent ectopic bone-inducing activity of bone morphogenetic protein-4/7 heterodimer. Biochem. Biophys. Res. Commun. 210: 670-677
63. 63 Suzuki A., Kaneko E., Maeda J. and Ueno N. (1997) Mesoderm induction by BMP-4 and -7 heterodimers. Biochem. Biophys. Res. Commun. 232: 153-156
64. 64 Nishimatsu S. and Thomson G. H. (1998) Ventral mesoderm induction and patterning by bone morphogenetic protein heterodimers in Xenopus embryos. Mech. Dev. 74: 75-88
65. 65 Jones C. M., Armes N. and Smith J. C. (1996) Signalling by TGF-β family members: short-range effects of Xnr-2 and BMP-4 contrast with the long-range effects of activin. Curr. Biol. 6: 1468-1475
66. 66 Dosch R., Gawantka V., Delius H., Blumenstock C. and Niehrs C. (1997) Bmp-4 acts as a morphogen in dorsoventral mesoderm patterning in Xenopus. Development 124: 2325-2334
67. 67 Neumann C. and Cohen S. (1997) Morphogens and pattern formation. Bioessays 19: 721-729
68. 68 Smith W. C. and Harland R. M. (1992) Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos. Cell 70: 829-840
69. 69 Zimmerman L. B., De Jesús-Escobar J. M. and Harland R. M. (1996) The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Cell 86: 599-606
70. 70 Fürthauer M., Thisse B. and Thisse C. (1999) Three different noggin genes antagonize the activity of bone morphogenetic proteins in the zebrafish embryo. Dev. Biol. 214: 181-196
71. 71 Connolly D. J., Patel K. and Cooke J. (1997) Chick noggin is expressed in the organizer and neural plate during axial development, but offers no evidence of involvement in primary axis formation. Int. J. Dev. Biol. 41: 389-396
72. 72 McMahon J. A., Takada S., Zimmerman L. B., Fan C. M., Harland R. M. and McMahon A. P. (1998) Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev. 12: 1438-1452
73. 73 Brunet L. J., McMahon J. A., McMahon A. P. and Harland R. M. (1998) Noggin, cartilage morphogenesis and joint formation in the mammalian skeleton. Science 280: 1455-1457
74. 74 Botchkarev V. A., Botchkareva N. V., Roth W., Nakamura M., Chen L. H., Herzog W. et al. (1999) Noggin is a mesenchymally derived stimulator of hair-follicle induction. Nat. Cell Biol. 1: 158-164
75. 75 Sasai Y., Lu B., Steinbeisser H., Geissert D., Gont L. K. and De Robertis E. M. (1994) Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes. Cell 79: 779-790
76. 76 Holley S. A., Jackson P. D., Sasai Y., Lu B., De Robertis E. M., Hoffmann F. M. et al. (1995) A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin. Nature 376: 249-253
77. 77 Schulte-Merker S., Lee K. J., McMahon A. P. and Hammerschmidt M. (1997) The zebrafish organizer requires chordino. Nature 387: 862-863
78. 78 Piccolo S., Sasai Y., Lu B. and De Robertis E. M. (1996) Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4. Cell 86: 589-598
79. 79 Shimell M. J., Ferguson E. L., Childs S. R. and O'Connor M. B. (1991) The Drosophila dorsal-ventral patterning gene tolloid is related to human bone morphogenetic protein 1. Cell 67: 469-481
80. 80 Ferguson E. L. and Anderson K. V. (1992) Localized enhancement and repression of the activity of the TGF-β family member, decapentaplegic, is necessary for dorsal-ventral pattern formation in the Drosophila embryo. Development 114: 583-597
81. 81 Maéno M., Xue Y., Wood T. I., Ong R. C. and Kung H.-F. (1993) Cloning and expression of cDNA encoding Xenopus laevis bone morphogenetic protein-1 during early embryonic development. Gene 134: 257-261
82. 82 Takahara K., Brevard R., Hoffman G. G., Suzuki N. and Greenspan D. S. (1996) Characterization of a novel gene product (mammalian tolloid-like) with high sequence similarity to mammalian tolloid/bone morphogenetic protein-1. Genomics 34: 157-165
83. 83 Lin J.-J., Maeda R., Ong R. C., Kim J., Lee L. M., Kung H.-f. et al. (1997) XBMP-1B (Xtld), a Xenopus homolog of dorso-ventral polarity gene in Drosophila, modifies tissue phenotypes of ventral explants. Dev. Growth Differ. 39: 43-51
84. 84 Piccolo S., Agius E., Lu B., Goodman S., Dale L. and De Robertis E. M. (1997) Cleavage of Chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity. Cell 91: 407-416
85. 85 Blader P., Rastegar S., Fischer N. and Strahle U. (1997) Cleavage of the BMP-4 antagonist chordin by zebrafish tolloid. Science 278: 1937-1940
86. 86 Scott I. C., Blitz I. L., Pappano W. N., Imamura Y., Clark T. G., Steiglitz B. M. et al. (1999) Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis. Dev. Biol. 213: 283-300
87. 87 Marqués G., Musacchio M., Shimell M. J., Wunnenberg-Stapleton K., Cho K. W. and O'Connor M. B. (1997) Production of a DPP activity gradient in the early Drosophila embryo through the opposing actions of the SOG and TLD proteins. Cell 91: 417-426
88. 88 Ashe H. L. and Levine M. (1999) Local inhibition and long-range enhancement of Dpp signal transduction by Sog. Nature 398: 427-431
89. 89 Nakamura T., Takio K., Eto Y., Shibai H., Titani K. and Sugino H. (1990) Activin-binding protein from rat ovary is follistatin. Science 247: 836-838
90. 90 Fainsod A., Deißler K., Yelin R., Marom K., Epstein M., Pillemer G. et al. (1997) The dorsalizing and neural inducing gene follistatin is an antagonist of BMP-4. Mech. Dev. 63: 39-50
91. 91 Iemura S., Yamamoto T. S., Takagi C., Uchiyama H., Natsume T., Shimasaki S. et al. (1998) Direct binding of follistatin to a complex of bone-morphogenetic protein and its receptor inhibits ventral and epidermal cell fates in early Xenopus embryo. Proc. Natl. Acad. Sci. USA 95: 9337-9342
92. 92 Bauer H., Meier A., Hild M., Stachel S., Economides A., Hazelett D. et al. (1998) Follistatin and noggin are excluded from the zebrafish organizer. Dev. Biol. 204: 488-507
93. 93 Albano R. M., Arkell R., Beddington R. S. P. and Smith J. C. (1994) Expression of inhibin subunits and follistatin during postimplantation mouse development: decidual expression of activin and expression of follistatin in primitive streak, somites and hindbrain. Development 120: 803-813
94. 94 Feijen A., Goumans M. J. and van den Eijnden-van Raaij A. J. M. (1994) Expression of activin subunits, activin receptors and follistatin in postimplantation mouse embryos suggests specific developmental functions for different activins. Development 120: 3621-3637
95. 95 Matzuk M. M., Lu N., Vogel H., Sellheyer K., Roop D. R. and Bradley A. (1995) Multiple defects and perinatal death in mice deficient in follistatin. Nature 374: 360-363
96. 96 Patel K., Makarenkova H. and Jung H.-S. (1999) The role of long range, local and direct signalling molecules during chick feather bud development involving the BMPs, follistatin and the Eph receptor tyrosine kinase Eph-A4. Mech. Dev. 86: 51-62
97. 97 Ozaki T. and Sakiyama S. (1993) Molecular cloning and characterization of a cDNA showing negative regulation in v-src-transformed 3Y1 rat fibroblasts. Proc. Natl. Acad. Sci. USA 90: 2593-2597
98. 98 Topol L. Z., Marx M., Laugier D., Bogdanova N. N., Boubnov N. V., Clausen P. A. et al. (1997) Identification of drm, a novel gene whose expression is suppressed in transformed cells and which can inhibit growth of normal but not transformed cells in culture. Mol. Cell Biol. 17: 4801-4810
99. 99 Bouwmeester T., Kim S., Sasai Y., Lu B. and De Robertis E. M. (1996) Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer. Nature 382: 595-601
100. 100 Hsu D. R., Economides A. N., Wang X., Eimon P. M. and Harland R. M. (1998) The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities. Mol. Cell 1: 673-683
101. 101 Pearce J. J., Penny G. and Rossant J. (1999) A mouse Cerberus/Dan-related gene family. Dev. Biol. 209: 98-110
102. 102 Zhu L., Marvin M. J., Gardiner A., Lassar A. B., Mercola M., Stern C. D. et al. (1999) Cerberus regulates left-right asymmetry of the embryonic head and heart. Curr. Biol. 9: 931-938
103. 103 Yokouchi Y., Vogan K. J., Pearse II R. V. and Tabin C. J. (1999) Antagonistic signaling by Caronte, a novel Cerberus-related gene, establishes left-right asymmetric gene expression. Cell 98: 573-583
104. 104 Rodriguez Esteban C., Capdevila J., Economides A. N., Pascual J., Ortiz A. and Izpisúa Belmonte J. C. (1999) The novel Cer-like protein Caronte mediates the establishment of embryonic left-right asymmetry. Nature 401: 243-251
105. 105 Nakamura Y., Ozaki T., Nakagawara A. and Sakiyama S. (1997) A product of DAN, a novel candidate tumour suppressor gene, is secreted into culture medium and suppresses DNA synthesis. Eur. J. Cancer 33: 1986-1990
106. 106 Piccolo S., Agius E., Leyns L., Bhattacharyya S., Grunz H., Bouwmeester T. et al. (1999) The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. Nature 397: 707-710
107. 107 Belo J. A., Bouwmeester T., Leyns L., Kertesz N., Gallo M., Follettie M. et al. (1997) Cerberus-like is a secreted factor with neutralizing activity expressed in the anterior primitive endoderm of the mouse gastrula. Mech. Dev. 68: 45-57
108. 108 Biben C., Stanley E., Fabri L., Kotecha S., Rhinn M., Drinkwater C. et al. (1998) Murine cerberus homologue mCer-1: a candidate anterior patterning molecule. Dev. Biol. 194: 135-151
109. 109 Shawlot W., Deng J. M. and Behringer R. R. (1998) Expression of the mouse cerberus-related gene, Cerr 1, suggests a role in anterior neural induction and somitogenesis. Proc. Natl. Acad. Sci. USA 95: 6198-6203
110. 110 Simpson E. H., Johnson D. K., Hunsicker P., Suffolk R., Jordan S. A. and Jackson I. J. (1999) The mouse Cer 1 (Cerberus related or homologue) gene is not required for anterior pattern formation. Dev. Biol. 213: 202-206
111. 111 Zúñiga A., Haramis A. P., McMahon A. P. and Zeller R. (1999) Signal relay by BMP antagonism controls the SHH FGF4 feedback loop in vertebrate limb buds. Nature 401: 598-602
112. 112 Capdevila J., Tsukui T., Rodríguez Esteban C., Zappavigna V. and Izpisúa Belmonte J. C. (1999) Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin. Mol. Cell 4: 839-849
113. 113 Merino R., Rodrigucz-Leon J., Macias D., Gañan Y., Economides A. N. and Hurle J. M. (1999) The BMP antagonist Gremlin regulates outgrowth, chondrogenesis and programmed cell death in the developing limb. Development 126: 5515-5522
114. 114 Iemuni S., Yamamoto T. S., Takagi C., Kobayashi H. and Ueno N. (1999) Isolation and characterization of bone morphogenetic protein-binding proteins from the early Xenopus embryo. J. Biol. Chem. 274: 26843-26849
115. 115 Selleck S. B. (1999) Overgrowth syndromes and the regulation of signaling complexes by proteoglycans. Am. J. Hum. Genet. 64: 372-377
116. 116 Jackson S. M., Nakato H., Sugiura M., Jannuzi A., Oakes R., Kaluza V. et al. (1997) dally, a Drosophila glypican, controls cellular responses to the TGF-β-relaled morphogen, Dpp. Development 124: 4113-4120
117. 117 Lin X. and Perrimon N. (1999) Dally cooperates with Drosophila Frizzled 2 to transduce Wingless signalling. Nature 400: 281-284
118. 118 Tsuda M., Kamimura K., Nakato H., Archer M., Staatz W., Fox B. et al. (1999) The cell-surface proteoglycan Dally regulates Wingless signalling in Drosophila. Nature 400: 276-280
119. 119 Onichtchouk D., Chen Y. G., Dosch R., Gawantka V., Delius H., Massagué J. et al. (1999) Silencing of TGF-β signalling by the pseudoreceptor BAMBI. Nature 401: 480-485
120. 120 Lecuit T. and Cohen S. M. (1998) Dpp receptor levels contribute to shaping the Dpp morphogen gradient in the Drosophila wing imaginal disc. Development 125: 4901-4907
121. 121 Tanimoto H., Itoh S., ten Dijke P. and Tabata T. (2000) Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discs. Mol. Cell. 5: 59-71
122. 122 Candia A. F., Watabe T., Hawley S. H. B., Onichtchouk D., Zhang Y., Derynck R. et al. (1997) Cellular interpretation of multiple TGF-β signals: intracellular antagonism between activin BVg1 and BMP-2/4 signaling mediated by Smads. Development 124: 4467-4480
123. 123 Galvin K. M., Donovan M. J., Lynch C. A., Meyer R. I., Paul R. J., Lorenz J. N. et al. (2000) A role for Smad6 in development and homeostasis of the cardiovascular system. Nat. Genet. 24: 171-174
124. 124 Imamura T., Takase M., Nishihara A., Oeda E., Hanai J., Kawabata M. et al. (1997) Smad6 inhibits signalling by the TCP-β superfamily. Nature 389: 622-626
125. 125 Souchelnytskyi S., Nakayama T., Nakao A., Morén A., Heldin C.-H., Christian J. L. et al. (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
126. 126 Inoue H., Imamura T., Ishidou Y., Takase M., Udagawa Y., Oka Y. et al. (1998) Interplay of signal mediators of Decapentaplegic (Dpp): molecular characterization of Mothers against dpp, Medea, and Daughters against dpp. Mol. Biol. Cell. 9: 2145-2156
127. 127 Hata A., Lagna G., Massagué J. and Hemmati-Brivanlou A. (1998) Smad6 inhibits BMP Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev. 12: 186-197
128. 128 Nakao A., Afrakhte M., Morén A., Nakayama T., Christian J. L., Heuchel R. et al. (1997) Identification of Smad7, a TGFβ-inducible antagonist of TGF-β signalling. Nature 389: 631-635
129. 129 Hayashi H., Abdollah S., Qiu Y., Cai J., Xu Y.-Y., Grinnell B. W. et al. (1997) The MAD-related protein Smad7 associates with the TGFβ receptor and functions as an antagonist of TGFβ signaling. Cell 89: 1165-1173
130. 130 Nakayama T., Snyder M. A., Grewal S. S., Tsuneizumi K., Tabata T. and Christian J. L. (1998) Xenopus Smad8 acts downstream of BMP-4 to modulate its activity during vertebrate embryonic patterning. Development 125: 857-867
131. 131 Tsuneizumi K., Nakayama T., Kamoshida Y., Kornberg T. B., Christian J. L. and Tabata T. (1997) Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature 389: 627-631
132. 132 Nakayama T., Gardner H., Berg L. K. and Christian J. L. (1998) Smad6 functions as an intracellular antagonist of some TGF-β family members during Xenopus embryogenesis. Genes Cells 3: 387-394
133. 133 Yamada M., Szendro P. I., Prokscha A., Schwartz R. J. and Eichele G. (1999) Evidence for a role of Smad6 in chick cardiac development. Dev. Biol. 215: 48-61
134. 134 Takase M., Imamura T., Sampath T. K., Takeda K., Ichijo H., Miyazono K. et al. (1998) Induction of Smad6 mRNA by bone morphogenetic proteins. Biochem. Biophys. Res. Commun. 244: 26-29
135. 135 Nagarajan R. P., Zhang J., Li W. and Chen Y. (1999) Regulation of Smad7 promoter by direct association with Smad3 and Smad4. J. Biol. Chem. 274: 33412-33418
136. 136 Ulloa L., Doody J. and Massagué J. (1999) Inhibition of transforming growth factor-ß/SMAD signalling by the interferon-γ STAT pathway. Nature 397: 710-713
137. 137 Zhu H., Kavsak P., Abdollah S., Wrana J. L. and Thomsen G. H. (1999) A SMAD ubiquitin ligasc targets the BMP pathway and affects embryonic pattern formation. Nature 400: 687-693
138. 138 Campbell G, and Tomlinson A. (1999) Transducing the Dpp morphogen gradient in the wing of Drosophila: regulation of Dpp targets by brinker. Cell 96: 553-562
139. 139 Jazwinska A., Kirov N., Wieschaus E., Roth S. and Rushlow C. (1999) The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation. Cell 96: 563-573
140. 140 Minami M., Kinoshita N., Kamoshida Y., Tanimoto H. and Tabata T. (1999) brinker is a target of Dpp in Drosophila that negatively regulates Dpp-dependent genes. Nature 398: 242-246
141. 141 Zimmerman C. M., Kariapper M. S. and Mathews L. S. (1998) Smad proteins physically interact with calmodulin. J. Biol. Chem. 273: 677-680
142. 142 Xu R.-H., Lechleider R. J., Shih H.-M., Hao C.-F., Sredni D., Roberts A. B. et al. (1999) Functional analysis of human Smad1: role of the amino-terminal domain. Biochem. Biophys. Res. Commun. 258: 366-373
143. 143 Shibuya H., Iwata H., Masuyama N., Gotoh Y., Yamaguchi K., Irie K. et al. (1998) Role of TAK1 and TAB1 in BMP signaling in early Xenopus development. EMBO J. 17: 1019-1028
144. 144 Yamaguchi K., Nagai S., Ninomiya-Tsuji J., Nishita M., Tamai K., Irie K. et al. (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
145. 145 Oeda E., Oka Y., Miyazono K. and Kawabata M. (1998) Interaction of Drosophila inhibitors of apoptosis with thick veins, a type I serine/threonine kinase receptor for decapentaplegic. J. Biol. Chem. 273: 9353-9356
146. 146 Kretzschmar M., Doody J. and Massagué J. (1997) Opposing BMP and EGF signalling pathways converge on the TGF-β family mediator Smad1. Nature 389: 618-622
147. 147 Neubüser A., Peters H., Balling R. and Martin G. R. (1997) Antagonistic interactions between FGF and BMP signaling pathways: a mechanism for positioning the sites of tooth formation. Cell 90: 247-255
148. 148 Xu R.-H., Ault K. T., Kim J., Park M.-J., Hwang Y.-S., Pong Y. et al. (1999) Opposite effects of FGF and BMP-4 on embryonic blood formation: roles of PV.I and GATA-2. Dev. Biol. 208: 352-361
149. 149 Nakashima K., Yanagisawa M., Arakawa H., Kimura N., Hisatsune T., Kawabata M. et al. (1999) Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science 284: 479-482
150. 150 Perrimon N. and McMahon A. P. (1999) Negative feedback mechanisms and their roles during pattern formation. Cell 97: 13-16