Smads and early developmental signaling by the TGFβ superfamily

Genes and Development

Volumn 12, Issue 16, 1998, Pages 2445-2462

  Whitman, Malcolm ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVIN; BONE MORPHOGENETIC PROTEIN; CALMODULIN; EPIDERMAL GROWTH FACTOR; FIBROBLAST GROWTH FACTOR; PROTEIN KINASE; SCATTER FACTOR; SMAD PROTEIN; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; UNCLASSIFIED DRUG;

CAENORHABDITIS ELEGANS; DIMERIZATION; DROSOPHILA; EMBRYO DEVELOPMENT; FEEDBACK SYSTEM; GENE EXPRESSION; GENETIC RECOMBINATION; MOLECULAR INTERACTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN FAMILY; REVIEW; SIGNAL TRANSDUCTION; TRANSACTIVATION; TRANSCRIPTION REGULATION; XENOPUS;

CAENORHABDITIS ELEGANS;

EID: 0032529159     PISSN: 08909369     EISSN: None     Source Type: Journal    
DOI: 10.1101/gad.12.16.2445     Document Type: Review

References (143)

1. Abdollah, S., M. Macías-Silva, T. Tsukazaki, H. Hayashi, L. Attisano, and J.L. Wrana. 1997. TβRI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2-Smad4 complex formation and signaling. J. Biol. Chem. 272: 27678-27685.
2. Arnone, M. and E. Davidson. 1997. The hardwiring of development: Organization and function of genomic regulatory systems. Development 124: 1851-1864.
3. Attisano, L. and J. Wrana. 1998. Mads and Smads in TGFβ signalling. Curr. Opin. Cell Biol. 10: 188-194.
4. Baker, J.C. and R.M. Harland. 1996. A novel mesoderm inducer, Madr2, functions in the activin signal transduction pathway. Genes & Dev. 10: 1880-1889.
5. Bodmer, R., L. Jan, and Y. Jan. 1990. A new homeobox-containing gene, msh-2, is transiently expressed early during mesoderm formation of Drosophila. Development 110: 661-669.
6. Bradley, L., D. Wainstock, and H. Sive. 1996. Positive and negative signals modulate formation of the Xenopus cement gland. Development 122: 2739-2750.
7. Brannon, M., M. Gomperts, L. Sumoy, R. Moon, and D. Kimelman. 1997. β-Catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus. Genes & Dev. 11: 2359-2370.
8. Candia, A., T. Watabe, S. Hawley, D. Onichtouk, Y. Zhang, R. Derynck, C. Niehrs, and K. Cho. 1997. Cellular interpretation of multiple TGFβ signals: Intracellular antagonism between activin/BVg1 and BMP-2/4 signaling mediated by Smads. Development 124: 4467-4480.
9. Carcamo, J., F. Weis, F. Ventura, R. Wieser, J.L. Wrana, L. Attisano, and J. Massagué. 1994. Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin. Mol. Cell. Biol. 14: 3810-3821.
10. Casellas, R. and A. Hemmati-Brivanlou. 1998. Xenopus Smad7 Inhibits both the Activin and BMP pathways and acts as a neural inducer. Dev. Biol. 198: 1-12.
11. Chen, X., M.J. Rubock, and M. Whitman. 1996. A transcriptional partner For Mad proteins in TGF-β signalling. Nature 383: 691-696.
12. Chen, X., E. Weisberg, V. Fridmacher, M. Watanabe, G. Naco, and M. Whitman. 1997. Smad4 and FAST-1 in the assembly of activin-response factor. Nature 389: 85-89.
13. Cho, K.W., B. Blumberg, H. Steinbesser, and E. DeRobertis. 1991. Molecular nature of Spemann's Organizer: The role of the Xenopus homeobox gene goosecoid. Cell 67: 1111-1120.
14. Cohen, P. 1997. The search for physiological substrates of MAP and SAP kinases in mammalian cells. Trends Cell Biol. 7: 353-361.
15. Conlon, F., K. Lyons, N. Takaesu, K. Barth, A. Kispert, B. Hermann, and E. Robertson. 1994. A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. Development 129: 1919-1928.
16. Conlon, F.L., C.M. Jones, and J.C. Smith. 1996. From mouse to frogs - Identification and functional analyses of genes required for induction and patterning of the mesoderm. Semin. Cell Dev. Biol. 7: 95-101.
17. Cornell, R.A. and D. Kimelman. 1994. Activin-mediated mesoderm induction requires FGF. Development 120: 453-462.
18. Dale, L., G. Howes, B.M.J. Price, and J.C. Smith. 1992. Bone morphogenetic protein 4: A ventralizing factor in Xenopus development. Development 115: 573-585.
19. Das, P., L. Maduzia, H. Wang, A. Finelli, S. Cho, M. Smith, and R. Padgett. 1998. The Drosophila gene Medea demonstrates the requirement for different classes of Smads in dpp signaling. Development 125: 1519-1528.
20. de Caestecker, M.P., P. Hemmati, S. Larisch-Bloch, R. Ajmera, A.B. Roberts, and R. J. Lechleider. 1997. Characterization of functional domains within Smad4/DPC4. J. Biol. Chem. 272: 13690-13696.
21. de Caestecker, M., W. Parks, C. Frank, P. Castagnino, D. Bottaro, A. Roberts, and R. Lechleider. 1998. Smad2 transduces common signals from receptor serine-threonine and tyrosine kinases. Genes & Dev. 12: 1587-1592.
22. Dennler, S., S. Itoh, D. Vivien, P. ten Dijke, S. Huet, and J. Gauthier. 1998. Direct binding of Smad3 and Smad4 to critical TGFβ inducible elements in the promoter of human plasminogen activator inhibitor-type I gene. EMBO J. 17: 3091-3100.
23. Derynck, R. and X.-H. Feng. 1997. TGFβ receptor signaling. Biochim. Biophys. Acta 1333: F105-F150.
24. Derynck, R., W.M. Gelbart, R.M. Harland, C.-H. Heldin, S.E. Kern, J. Massagué, D.A. Melton, M. Moldzik, R.W. Padgett, A.B. Roberts, J. Smith, G.H. Thomsen, B. Vogelstein, and X.-F. Wang. 1996. Nomenclature: Vertebrate mediators of TGF-β family signals. Cell 87: 173.
25. Dick, A., W. Risau, and H. Drexler. 1998. Expression of Smad1 and Smad2 during embryogenesis suggests a role in organ development. Dev. Dyn. 211: 293-305.
26. Dohrmann, C.E., A. Hemmati-Brivanlou, G.H. Thomsen, A. Fields, T. Woolf, and D. Melton. 1993. Expression of activin mRNA during early development in Xenopus laevis. Dev. Biol. 157: 474-483.
27. Dosch, R., V. Gawantka, H. Delius, C. Blumenstock, and C. Niehrs. 1997. Bmp-4 acts as a morphogen in dorsoventral mesoderm patterning in Xenopus. Development 124: 2325-2334.
28. Dyson, S. and J. Gurdon. 1998. The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors. Cell 93: 557-568.
29. Eppert, K., S.W. Scherer, H. Ozcelik, R. Pirone, P. Hoodless, H. Kim, L.C. Tsui, B. Bapat, S. Gallinger, I.L. Andrulis, G.H. Thomsen, J.L. Wrana, and L. Attisano. 1996. Madr2 maps to 18q21 and encodes a Tgf-β-regulated Mad-related protein that is functionally mutated in colorectal carcinoma. Cell 86: 543-552.
30. Epstein, R., B. Druker, T. Roberts, and C. Stiles. 1992. Synthetic phosphopeptides yield activation-specific antibodies to the c-erbB2 receptor. Proc. Nat. Acad. Sci. 89: 10435-10439.
31. Estevez, M., L. Attisano, J. Wrana, P. Albert, J. Massagué, and D. Riddle. 1993. The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development. Nature 365: 644-649.
32. Ferguson, E. 1996. Conservation of dorsal-ventral patterning in arthropods and chordates. Curr. Opin. Genet. Dev. 6: 424-431.
33. Ferguson, E. and K. Anderson. 1992. Decapentaplegic acts as a morphogen to organize dorsal-ventral patern in the Drosophila embryo. Cell 54: 95-104.
34. Frasch, M. 1995. Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early Drosophila embryo. Nature 374: 464-467.
35. Gabay, L., R. Seger, and B. Shilo. 1997. MAP kinase in situ activation atlas during Drosophila embryogenesis. Development 124: 3535-3541.
36. Ganan, Y., D. Macías, M. Duterque-Coquillaud, M. Ros, and J. Hurle. 1996. Role of TGFβs and BMPs controlling the position of the digits and the areas of interdigital cell death in the developing chick limb autopod. Development 122: 2349-2357.
37. Gawantka, V., H. Delius, K. Hirschfeld, C. Blumenstock, and C. Niehrs. 1995. Antagonizing the Spermann Organizer - Role of the homeobox gene Xvent-1. EMBO J. 14: 6268-6279.
38. Gelbart, W. 1989. The decapentaplegic gene: A TGFβ homolog controlling pattern formation in Drosophila. Development (Suppl.) 107: 65-74.
39. Graff, J.M., R.S. Thies, J.J. Song, A.J. Celeste, and D.A. Melton. 1994. Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo. Cell 79: 169-179.
40. Graff, J.M., A. Bansal, and D.A. Melton. 1996. Xenopus Mad proteins transduce distinct subsets of signals for the Tgf-β superfamily. Cell 85: 479-487.
41. Graham, A. and A. Lumsden. 1996. Patterning the neural crest. Biochem. Soc. Symp. 62: 77-83.
42. Green, J.B.A. and J.C. Smith. 1990. Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate. Nature 347: 391-394.
43. Green, J.B.A., H.V. New, and J.C. Smith. 1992. Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm. Cell 71: 731-739.
44. Green, J.B., J.C. Smith, and J.C. Gerhart. 1994. Slow emergence of a multithreshold response to activin requires cell-contact-dependent sharpening but not prepattern. Development 120: 2271-2278.
45. Grimm, S. and G. Pflugfelder. 1996. Control of the gene optomotor-blind in Drosophila wing development by decapentaplegic and wingless. Science 271: 1601-1604.
46. Gurdon, J.B., P. Harger, A. Mitchell, and P. Lemaire. 1994. Activin signaling and response to a morphogen gradient. Nature 371: 487-492.
47. Harland, R. and J. Gerhart. 1997. Formation and function of Spemann's Organizer. Annu. Rev. Cell Dev. Biol. 13: 611-667.
48. Hata, K., R.S. Lo, D. Wotton, G. Lagna, and J. Massagué. 1997. Mutations increasing autoinhibition inactivate tumour suppressors Smad2 and Smad4. Nature 388: 82-87.
49. Hata, A., G. Lagna, J. Massagué, and A. Hemmati-Brivanlou. 1998. Smad6 inhibits BMP/Smadl signaling by specifically competing with the Smad4 tumor suppressor. Genes & Dev. 12: 186-197.
50. Hayashi, H., S. Abdollah, Y. Qui, J. Cai, Y. Xu, B. Grinnell, M. Richardson, J. Topper, M. Gimbrone, J. Wrana, and D. Falb. 1997. The Mad-related protein Smad7 associates with the TGF-β receptor and functions as an antagonist of TGF-β signaling. Cell 89: 1165-1173.
51. Heldin, C.-H., K. Miyazono, and P. ten Dijke. 1997. TGFβ signalling from cell membrane to nucleus through Smad proteins. Nature 390: 465-471.
52. Hemmati-Brivanlou, A. and D.A. Melton. 1992. A truncated activin receptor dominantly inhibits mesoderm induction and formation of axial structures in Xenopus embryos. Nature 359: 609-614.
53. Hemmati-Brivanlou, A. and G.H. Thomsen. 1995. Ventral mesodermal patterning in Xenopus embryos - Expression patterns and activities of Bmp-2 and Bmp-4. Dev. Genet. 17: 78-89.
54. Holley, S., P. Jackson, Y. Sasai, B. Lu, E.D. Robertis, F. Hoffman, and E. Ferguson. 1995. A conserved system for dorsal-ventral patterning in insects and vertebrates involving short gastrulation and chordin. Nature 376: 249-253.
55. Hoodless, P.A., T. Haerry, S. Abdollah, M. Stapleton, M.B. O'Connor, L. Attisano, and J.L.Wrana. 1996. MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Cell 85: 489-500.
56. Huang, H.C., L.C. Murtaugh, P.D. Vize, and M. Whitman. 1995. Identification of a potential regulator of early transcriptional responses to mesoderm inducers in the frog embryo. EMBO J. 14: 5965-5973.
57. Hudson, J., S. Podos, K. Keith, S. Simpson, and E. Ferguson. 1998. Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4. Development 125: 1407-1420.
58. Imamura, T., M. Takase, A. Nishihara, E. Oeda, J.-I. Hanai, M. Kawabata, and K. Miyazono. 1997. Smad6 inhibits signalling by the TGFβ superfamily. Nature 389: 622-626.
59. Jones, C.M., K.M. Lyons, P.M. Lapan, C. Wright, and B. Hogan. 1992. DVR-4 (bone morphogenetic protein-4) as a posteroventralizing factor in Xenopus mesoderm induction. Development 115: 639-647.
60. Kim, J., K. Johnson, H. Chen, S. Carroll, and A. Laughon. 1997. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Nature 388: 304-308.
61. Kingsley, D. 1994. The TGFβ superfamily: New members, new receptors, and new genetic tests of function in different organisms. Genes & Dev. 8: 133-146.
62. Knecht, A. and R. Harland. 1997. Mechanisms of dorsal-ventral patterning in noggin induced neural tissue. Development 124: 2477-2488.
63. Kretzschmar, M., J. Doody, and J. Massagué. 1997a. Opposing BMP and EGF signalling pathways converge on the TGF-β family mediator Smad1. Nature 389: 618-622.
64. Kretzschmar, M., F. Liu, A. Hata, J. Doody, and J. Massagué 1997b. The TGF-β family mediator Smadl is phosphorylated directly and activated functionally by the BMP receptor kinase. Genes &. Dev. 11: 984-995.
65. LaBonne, C. and M. Whitman. 1994. Mesoderm induction by activin requires FGF-mediated intracellular signals. Development 120: 463-472.
66. _. 1997. Localization of MAP kinase activity in early Xenopus embryos: Implications for endogenous FGF signaling. Dev. Biol. 183: 9-20.
67. LaBonne, C., B. Burke, and M. Whitman. 1995. Role of MAP kinase in mesoderm induction and axial patterning during Xenopus development. Development 121: 1475-1486.
68. Lagna, G., A. Hata, A. Hemmati-Brivanlou, and J. Massagué. 1996. Partnership between DPC4 and SMAD proteins in TGF-β signalling pathways. Nature 383: 832-836.
69. Latinkic, B., M. Umbhauer, K. Neal, W. Lerchner, J. Smith, and V. Cunliffe. 1997. The Xenopus Brachyury promoter is activated by FGF and low concentrations of activin and suppressed by high concentrations of activin and by paired-type homeodomains. Genes & Dev. 11: 3265-3276.
70. Laurent, M., I. Blitz, C. Hashimoto, U. Rothbacher, and K. Cho. 1997. The Xenopus homeobox gene twin mediates Wnt isduction of goosecoid in establishment of Spemann's organizer. Development 124: 4905-4916.
71. Lecuit, T., W. Brook, M. Ng, M. Calleja, H. Sun, and S. Cohen. 1996. Two distinct mechanisms for long-range patterning by decapentaplegic in the Drosophila wing. Nature 381: 387-393.
72. Liu, F., A. Hata, J.C. Baker, J. Doody, T. Carcamo, R.M. Harland, and J. Massagué. 1996. A human Mad protein acting as a BMP-regulated transcriptional activator. Nature 381: 620-623.
73. Liu, F., C. Pouponnot, and J. Massagué. 1997. Dual role of the Smad4/DPC4 tumor suppressor in TGFβ inducible transcriptional complexes. Genes & Dev. 11: 3157-3167.
74. Lo, R., Y. Chen, Y. Shi, N. Pavletich, and J. Massagué. 1998. The L3 Loop: A structural motif determining specific interactions between SMAD proteins and TGFβ receptors. EMBO J. 17: 996-1005.
75. Lopez-Casillas, F., J. Wrana, and J. Massagué. 1993. Betaglycan presents ligand to the TGFβ signaling receptor. Cell 73: 1435-1444.
76. Lustig, K., K. Kroll, E. Sun, R. Ramos, H. Elmendorf, and M. Kirschner. 1996. A Xenopus nodal-related gene that acts in synergy with noggin to induce secondary axis and notochord formation. Development 122: 3275-3282.
77. Macias-Silva, M., S. Abdollah, P.A. Hoodless, R. Pirone, L. Attisano, and J.L. Wrana. 1996. Madr2 is a substrate of the Tgf-β receptor and its phosphorylation is required for nuclear accumulation and signaling. Cell 87: 1215-1224.
78. Massagué, J. 1998. TGFβ signal transduction. Annu. Rev. Biochem. (in press).
79. Mehler, M., P. Mabie, D. Zhang, and J. Kessler. 1997. Bone morphogenetic proteins in the nervous system. Trends Neurosci. 20: 309-317.
80. Mishina, Y., A. Suzuki, N. Ueno, and R. Behringer. 1995. Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes & Dev. 9: 3027-3037.
81. Moses, H.L. and R. Serra. 1996. Regulation of differentiation by TGFβ. Curr. Opin. Genet. Dev. 6: 581-596.
82. Nakao, A., M. Afrakhte, A. Moren, T. Nakayama, J. Christian, R. Heuchel, S. Itoh, M. Kawabata, N. Heldin, C. Heldin, and P. ten Dijke. 1997a. Identification of Smad7, a TGFβ inducible antagonist of tGFβ signaling. Nature 389: 631-635.
83. Nakao, A., T. Imamura, S. Souchelnytskyi, M. Kawabata, A. Ishisaki, E. Oeda, K. Tamaki, J.-I. Hanai, C.-H. Heldin, K. Miyazono, and P. ten Dijke. 1997b. TGFβ receptor mediated signaling through Smad2, Smad3, and Smad4. EMBO J. 16: 5353-5362.
84. Nakayama, T., M. Snyder, S. Grewal, K. Tsuneizumi, T. Tabata, and J. Christian. 1998. Xenopus Smad8 acts downstream of BMP-4 to modulate its activity during vertebrate embryonic patterning. Development 125: 857-867.
85. Nellen, D., R. Burke, G. Struhl, and K. Basler. 1996. Direct and long range action of a DPP morphogen gradient. Cell 85: 357-368.
86. Neubuser, A., H. Peters, R. Balling, and G. Martin. 1997. Antagonistic interactions between FGF and BMP signaling pathways: A mechanism for positioning the sites of tooth formation. Cell 90: 247-255.
87. Neumann, C. and S. Cohen. 1997. Morphogens and pattern formation. BioEssays 19: 721-729.
88. Newfeld, S.J., E.H. Chartoff, J.M. Graff, D.A. Melton, and W.M. Gelbart. 1996. Mothers against Dpp encodes a conserved cytoplasmic protein required in Dpp/Tgf-β responsive cells. Development 122: 2099-2108.
89. Newfeld, S., A. Mehra, M. Singer, J. Wrana, L. Attisano, and W. Gelbart. 1997. Mothers against dpp participates in a DPP/ TGFβ responsive serine-threonine kinase signal transduction cascade. Development 124: 3167-3176.
90. Niki, I., H. Yokokura, T. Sudo, M. Kato, and H. Hidaka. 1996. Ca2+ signaling and intracellular Ca2+ binding proteins. J. Biochem. 120: 685-698.
91. Nishimatsu, S., A. Suzuki, A. Shoda, K. Murakami, and N. Ueno. 1992. Genes for bone morphogenetic proteins are differentially transcribed in early amphibian embryos. Biochem. Biophys. Res. Commun. 186: 1487-1495.
92. Nishimatsu, S., K. Takebayashi, A. Suzuki, K. Murakami, and N. Ueno. 1993. Immunodetection of Xenopus bone morphogenetic protein-4 in early embryos. Growth Factors 8: 173-176.
93. Niswander, L. and G. Martin. 1993. FGF-4 and BMP-2 have opposite effects on limb growth. Nature 361: 68-71.
94. Nomura, M. and E. Li. 1998. Roles for Smad2 in mesoderm formation, left right patterning, and craniofacial development in mice. Nature 393: 786-789.
95. Oda, S., S. Nishimatsu, K. Murakami, and N. Ueno. 1995. Molecular cloning and functional analysis of a new activin b subunit: A dorsal mesoderm-inducing acitivity in Xenopus. Biochem. Biophys. Res. Comm. 210: 581-588.
96. Oft, M., J. Peli, C. Rudaz, H. Schwarz, H. Beug, and E. Reichmann. 1996. TGF-β1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes & Dev. 10: 2462-2477.
97. Patterson, G., A. Koweek, A. Wong, L. Yanxia, and G. Ruvkun. 1997. The daf-3 smad protein antagonizes TGF-β-related receptor signaling in the Caenorhabditis elegans dauer pathway. Genes & Dev. 11: 2679-2690.
98. Piccolo, S., Y. Sasai, B. Lu, and E. DeRobertis. 1996. Dorsoventral patterning in Xenopus inhibition of ventral signals by binding of chordin to BMP-4. Cell 86: 589-598.
99. Piccolo, S., E. Agius, B. Lu, S. Goodman, L. Dale, and E.M. DeRobertis. 1997. Cleavage of chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann Organizer activity. Cell 91: 407-416.
100. Raftery, L., V. Twombly, K. Wharton, and W. Gelbart. 1995. Genetic screens to identify elements of the decapentaplegic signaling pathway. Genetics 139: 241-254.
101. Re'em-Kalma, Y., T. Lamb, and D. Frank. 1995. Competition between noggin and bone morphogenetic protein 4 activities may regulate dorsalization during Xenopus development. Proc. Natl. Acad. Sci. 92: 12141-12145.
102. Roberts, A.B. and M.B. Sporn. 1993. Physiological actions and clinical applications of transforming growth factor-β. Growth Factors 8: 1-9.
103. Rosa, F.M. 1989. Mix. 1, a homeobox mRNA inducible by mesoderm inducers, is expressed mostly in the presumptive endodermal cells of Xenopus embryos. Cell 57: 965-974.
104. Sasai, Y., B. Lu, H. Steinbeisser, D. Geissert, L. Gont, and E.M. De Robertis. 1994. Xenopus chordin: A novel dorsalizing factor activated by organizer-specific homeobox genes. Cell 79: 779-790.
105. Savage, C., P. Das, A.L. Finelli, S.R. Townsend, C.Y. Sun, S.E. Baird, and R. W. Padgett. 1996. Caenorhabditis elegans genes Sma2, Sma-3, and Sma-4 define a conserved family of transforming growth factor β pathway components. Proc. Natl. Acad. Sci. 93: 790-794.
106. Schmidt, J., V. Francois, E. Bier, and D. Kimelman. 1995a. Drosophila short gastrulation induces an ectopic axis in Xenopus: Evidence for conserved mechanisms of dorsal-ventral patterning. Development 121: 4319-4328.
107. Schmidt, J.E., A. Suzuki, N. Ueno, and D. Kimelman. 1995b. Localized BMP-4 mediates dorsal/ventral patterning in the early Xenopus embryo. Dev. Biol. 169: 37-50.
108. Schulte-Merker, S., J.C. Smith, and L. Dale. 1994. Effects of truncated activin and FGF receptors and of follistatin on the inducing activities of BVg1 and activin: Does activin play a role in mesoderm induction? EMBO J. 13: 3533-3541.
109. Sekelsky, J.J., S.J. Newfeld, L.A. Raftery, E.H. Chartoff, and W.M. Gelhart. 1995. Genetic characterization and cloning of Mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics 139: 1347-1358.
110. Shi, Y., A. Hata, R.S. Lo, J. Massagué, and N.P. Pavletich. 1997. A structural basis for mutational inactivation of the tumour suppressor Smad4. Nature 388: 87-93.
111. Shibuya, H., H. Iwata, N. Masuyama, Y. Gotoh, K. Yamaguchi, K. Irie, K. Matsumoto, E. Nishida, and N. Ueno. 1998. Role of TAK1 and TAB1 in BMP signaling in early Xenopus development. EMBO J. 17: 1019-1028.
112. Sirard, C., J.L. de la Pompa, A. Elia, A. Itie, C. Mirtsos, A. Cheung, S. Hahn, A. Wakeham, L. Schwartz, S. Kern, J. Rossant, and T. Mak. 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.
113. Sive, H.L., K. Hattori, and H. Weintraub. 1989. Progressive detemination during formation of the anteroposterior axis of Xenopus laevis. Cell 58: 171-180.
114. Smith, J.C. 1987. A mesoderm-inducing factor is produced by a Xenopus cell line. Development 99: 3-14.
115. 467 in the C-terminus of Smad2 mediates interaction with Smad4 and is required for TGFβ signaling. J. Biol. Chem. 272: 28107-28115.
116. Steinbach, O., A. Wolffe, and R. Rupp. 1997. Somatic linker histones cause loss of meosdermal competence in Xenopus. Nature 389: 395-399.
117. Suzuki, A., R.S. Thies, N. Yamaji, J.J. Song, J.M. Wozney, K. Murakami, and N. Ueno. 1994. A truncated bone morphogenetic protein receptor affects dorsal-ventral patterning in the early Xenopus embryo. Proc. Natl. Acad. Sci. 91: 10255-10259.
118. Suzuki, A., C. Chang, J.M. Yingling, X.F. Wang, and A. Hemmati-Brivanlou. 1997a. Smad5 induces ventral fates in Xenopus embryo. Dev. Biol. 184: 402-405.
119. Suzuki, A., E. Kaneko, N. Ueno, and A. Hemmati-Brivanlou. 1997b. Regulation of epidermal induction by BMP2 and BMP7. Dev. Biol. 189: 112-122.
120. Tanabe, Y. and T. Jessell. 1997. Diversity and patterning in the developing spinal cord. Science 274: 1115-1122.
121. Thomsen, G. and D. Melton. 1993. Processed Vg1 protein is an axial mesoderm inducer in Xenopus. Cell 74: 433-441.
122. Thomsen, G.H. 1996. Xenopus mothers against decapentaplegic is an embryonic ventralizing agent that acts downstream of the Bmp-2/4 receptor. Development 122: 2359-2366.
123. Topper, J., J. Cai, Y. Qiu, K. Anderson, Y. Xu, J. Deeds, R. Feeley, C. Gimeno, E. Woolf, O. Tayber, G. Mays, B. Sampson, F. Schoen, M. Gimbrone, and D. Falb. 1997. Vascular MADs: Two novel MAD-related genes selectively inducible by flow in human vascular endothelium. Proc. Natl. Acad. Sci. 94: 9314-9319.
124. Tsuneizumi, K., T. Nakayama, Y. Kamoshida, T. Kornberg, J. Christian, and T. Tabata. 1997. Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature 389: 627-631.
125. Waldrip, W., E. Bikoff, P. Hoodless, J. Wrana, and E. Robertson. 1998. Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo. Cell 92: 797-808.
126. Wall, N.A. and B.L.M. Hogan. 1994. TGF-β related genes in development. Curr. Biol. 4: 517-522.
127. Watabe, T., S. Kim, A. Candia, U. Rothbacher, C. Hashimoto, K. Inoue, and K.W.Y. Cho. 1995. Molecular mechanisms of Spemanns organizer formation - Conserved gzrowth factor synergy between Xenopus and mouse. Genes &. Dev. 9: 3038-3050.
128. Weeks, D.L. and D.A. Melton. 1987. A maternal mRNA localized to the vegetal hemisphere in Xenopus eggs codes for a growth factor related to TGF-β. Cell 51: 861-867.
129. Wharton, K., R. Ray, and W. Gelbart. 1993. An activity gradient of decapentaplegic is required for dorsal-ventral patterning in the Drosophila embryo. Development 117: 807-822.
130. Wiersdorff, V., T. Lecuit, S.M. Cohen, and M. Mlodzik. 1996. Mad acts downstream of Dpp receptors, revealing a differential requirement for Dpp signaling in initiation and propagation of morphogenesis in the Drosophila eye. Development 122: 2153-2162.
131. Wilson, P.A., G. Lagna, A. Suzuki, and A. Hemmati-Brivanlou. 1997. Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smadl. Development 124: 3177-3184.
132. Winnier, G., M. Blessing, P.A. Labosky, and B.L. Hogan. 1995. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes & Dev. 9: 2105-2116.
133. Wisotzkey, R., A. Mehra, D. Sutherland, L. Dobens, X. Liu, C. Dohrmann, L. Attisano, and L. Raftery. 1998. Medea is a Drosophila Smad4 homolog that is differentially required to potentiate DPP responses. Development 125: 1433-1445.
134. Xu, X., Z. Yin, J. Hudson, E. Ferguson, and M. Frasch. 1998. Smad proteins act in combination with synergistic and antagonistic regulators to target Dpp responses to the Drosophila mesoderm. Genes & Dev. 12: 2354-2370.
135. Yamaguchi, K., K. Shirakabe, H. Shibuya, K. Irie, I. Oishi, N. Ueno, T. Taniguchi, E. Nishida, and K. Matsumoto. 1995. Identification of a member of the MAPKKK family as a potential mediator of TGF-β signal transduction. Science 270: 2008-2011.
136. Yang, X., C. Li, X. Xu, and C. Deng. 1998. The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice. Proc. Natl. Acad. Sci. 95: 3667-3672.
137. Yingling, J., P. Das, C. Savage, C. Xhang, and R. Padgett. 1996. Mammalian dwarfins are phosphorylated in response to TGFβ and are implicated in the control of cell growth. Proc. Natl. Acad. Sci. 93: 8940-8944.
138. Yingling, J., M. Datto, C. Wong, J. Frederick, N. Liberati, and X. Wang. 1997. Tumor suppressor Smad4 is a transforming growth factor inducible DNA binding protein. Mol. Cell. Biol. 17: 7019-7028.
139. Zawel, L., J. Dai, P. Buckhaults, S. Zhou, K. Kinzler, B. Vogelstein, and S. Kern. 1998. Human Smad3 and Smad4 are sequence specific transcription activators. Mol. Cell 1: 611-617.
140. Zhang, Y., X.H. Feng, R.Y. Wu, and R. Derynck. 1996. Receptor-associated Mad homologues synergize as effectors of the Tgf-β response. Nature 383: 168-172.
141. Zhang, Y., T. Musci, and R. Derynck. 1997. The tumor suppressor Smad4/DPC 4 as a central mediator of Smad function. Curr. Biol. 7: 270-276.
142. Zimmerman, C., M. Kariapper, and L. Mathews. 1998. Smad proteins physically interact with calmodulin. J. Biol. Chem. 273: 677-680.
143. Zimmerman, L.B., L.M. De Jesus-Escobar, and R.M. Harland. 1996. The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Cell 86: 599-606.