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Smad Signal Transduction pp 55–73Cite as

Smads In Drosophila – Interpretation Of Graded Signals In Vivo

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Part of the book series: Proteins and Cell Regulation ((PROR,volume 5))

Abstract

Drosophila has both BMP and Activin signaling pathways, but little is known about the functions of the Activin/TGF-β class of signals in this organism. BMP signaling has been intensively studied in this organism, and Drosophila continues to stand as a paradigm for understanding the functions of BMPs in development. Drosophila BMPs can induce different cell fates at different concentrations, a critical property for extracellular signals that direct spatial patterning of tissues. Although the endogenous BMP ligands are difficult to detect, spatial patterns of cells with phosphorylated R-Smad and nuclear co-Smad reveal the graded distribution of BMP activity in the embryonic ectoderm and the wing primordium. The question of how cells interpret different levels of BMP activity has been a major focus for studies of Smads in Drosophila. We review the general modes for Smad regulation of BMP target genes, including direct repression of gene expression, indirect induction through release from repression, and direct activation of gene expression. These studies integrate the mechanisms for gene regulation by Smads with the logic of spatial and temporal regulation of development by BMPs

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References

  • Adachi-Yamada, T., and O’Connor, M.B., 2004, Mechanisms for removal of developmentally abnormal cells: cell competition and morphogenetic apoptosis. J Biochem (Tokyo) 136: 13-17.

    Google Scholar 

  • Affolter, M., Marty, T., Vigano, M.A., and Jazwinska, A., 2001, Nuclear interpretation of Dpp signaling in Drosophila. EMBO J 20: 3298-3305.

    Article  PubMed  CAS  Google Scholar 

  • Ashe, H.L., 2005, BMP signalling: synergy and feedback create a step gradient. Curr Biol 15: R375-377.

    Article  PubMed  CAS  Google Scholar 

  • Ashe, H.L., Mannervik, M., and Levine, M., 2000, Dpp signaling thresholds in the dorsal ectoderm of the Drosophila embryo. Development 127: 3305-3312.

    PubMed  CAS  Google Scholar 

  • Barolo, S., and Posakony, J., 2002, Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev 16: 1167-1181.

    Article  PubMed  CAS  Google Scholar 

  • Barrio, R., and de Celis, J.F., 2004, Regulation of spalt expression in the Drosophila wing blade in response to the Decapentaplegic signaling pathway. Proc Natl Acad Sci U S A 101: 6021-6026.

    Article  PubMed  CAS  Google Scholar 

  • Casanueva, M.O., and Ferguson, E.L., 2004, Germline stem cell number in the Drosophila ovary is regulated by redundant mechanisms that control Dpp signaling. Development 131: 1881-1890.

    Article  PubMed  CAS  Google Scholar 

  • Curtiss, J., Halder, G., and Mlodzik, M., 2002, Selector and signalling molecules cooperate in organ patterning. Nat Cell Biol 4: E48-51.

    Article  PubMed  CAS  Google Scholar 

  • Dai, H., Hogan, C., Gopalakrishnan, B., Torres-Vazquez, J., Nguyen, M., Park, S., Raftery, L.A., Warrior, R., and Arora, K., 2000, The zinc finger protein schnurri acts as a Smad partner in mediating the transcriptional response to decapentaplegic. Dev Biol 227: 373-387.

    Article  PubMed  CAS  Google Scholar 

  • Dobens, L.L., Peterson, J., Treisman, J., and Raftery, L.A., 2000, Drosophila bunched integrates opposing DPP and EGF signals to set the operculum boundary. Development 127: 745-754.

    PubMed  CAS  Google Scholar 

  • Domingos, P.M., Brown, S., Barrio, R., Ratnakumar, K., Frankfort, B.J., Mardon, G., Steller, H., and Mollereau, B., 2004, Regulation of R7 and R8 differentiation by the spalt genes. Dev Biol 273: 121-133.

    Article  PubMed  CAS  Google Scholar 

  • Entchev, E.V., Schwabedissen, A., and Gonzalez-Gaitan, M., 2000, Gradient formation of the TGF-β homolog Dpp. Cell 103: 981-991.

    Article  PubMed  CAS  Google Scholar 

  • Gao, S., Steffen, J., and Laughon, A., 2005, Dpp-responsive silencers are bound by a trimeric Mad-Medea complex. J Biol Chem 280: 36158-36164.

    Article  PubMed  CAS  Google Scholar 

  • Gibson, M.C., and Perrimon, N., 2005, Extrusion and death of DPP/BMP-compromised epithelial cells in the developing Drosophila wing. Science 307: 1785-1789.

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Gaitan, M., 2003, Signal dispersal and transduction through the endocytic pathway. Nat Rev Mol Cell Biol 4: 213-224.

    Article  PubMed  CAS  Google Scholar 

  • Gurdon, J.B., and Bourillot, P.Y., 2001, Morphogen gradient interpretation. Nature 413: 797-803.

    Article  PubMed  CAS  Google Scholar 

  • Halfon, M.S., Carmena, A., Gisselbrecht, S., Sackerson, C.M., Jimenez, F., Baylies, M.K., and Michelson, A.M., 2000, Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors. Cell 103: 63-74.

    Article  PubMed  CAS  Google Scholar 

  • Hipfner, D.R., and Cohen, S.M., 2004, Connecting proliferation and apoptosis in development and disease. Nat Rev Mol Cell Biol 5: 805-815.

    Article  PubMed  CAS  Google Scholar 

  • Hogan, B.L.M., 1996, Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev 10: 1580-1594.

    PubMed  CAS  Google Scholar 

  • Jazwinska, A., Rushlow, C., and Roth, S., 1999, The role of brinker in mediating the graded response to Dpp in early Drosophila embryos. Development 126: 3323-3334.

    PubMed  CAS  Google Scholar 

  • Johnston, L.A., and Gallant, P., 2002, Control of growth and organ size in Drosophila. Bioessays 24: 54-64.

    Article  PubMed  CAS  Google Scholar 

  • Jorgensen, P., and Tyers, M., 2004, How cells coordinate growth and division. Curr Biol 14: R1014-1027.

    Article  PubMed  CAS  Google Scholar 

  • Kawase, E., Wong, M.D., Ding, B.C., and Xie, T., 2004, Gbb/Bmp signaling is essential for maintaining germline stem cells and for repressing bam transcription in the Drosophila testis. Development 131: 1365-1375.

    Article  PubMed  CAS  Google Scholar 

  • Kirkpatrick, H., Johnson, K., and Laughon, A., 2001, Repression of dpp targets by binding of brinker to mad sites. J Biol Chem 276: 18216-18222.

    Article  PubMed  CAS  Google Scholar 

  • Lee-Hoeflich, S.T., Zhao, X., Mehra, A., and Attisano, L., 2005, The Drosophila type II receptor, Wishful thinking, binds BMP and myoglianin to activate multiple TGFβ family signaling pathways. FEBS Lett 579: 4615-4621.

    Article  PubMed  CAS  Google Scholar 

  • Marques, G., 2005, Morphogens and synaptogenesis in Drosophila. J Neurobiol 64: 417-434.

    Article  PubMed  CAS  Google Scholar 

  • Martin-Castellanos, C., and Edgar, B.A., 2002, A characterization of the effects of Dpp signaling on cell growth and proliferation in the Drosophila wing. Development 129: 1003-1013.

    PubMed  CAS  Google Scholar 

  • Marty, T., Muller, B., Basler, K., and Affolter, M., 2000, Schnurri mediates dpp-dependent repression of brinker transcription. Nat Cell Biol 2: 745-749.

    Article  PubMed  CAS  Google Scholar 

  • Meinhardt, H., and Roth, S., 2002, Developmental biology: sharp peaks from shallow sources. Nature 419: 261-262.

    Article  PubMed  CAS  Google Scholar 

  • Mizutani, C.M., Nie, Q., Wan, F.Y., Zhang, Y.T., Vilmos, P., Sousa-Neves, R., Bier, E., Marsh, J.L., and Lander, A.D., 2005, Formation of the BMP activity gradient in the Drosophila embryo. Dev Cell 8: 915-924.

    Article  PubMed  CAS  Google Scholar 

  • Moreno, E., Basler, K., and Morata, G., 2002, Cells compete for Decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 416: 755-759.

    Article  PubMed  CAS  Google Scholar 

  • Morisato, D., and Anderson, K.V., 1995, Signaling pathways that establish the dorsal-ventral pattern of the Drosophila embryo. Annu Rev Genet 29: 371-399.

    Article  PubMed  CAS  Google Scholar 

  • Müller, B., Hartmann, B., Pyrowolakis, G., Affolter, M., and Basler, K., 2003, Conversion of an extracellular Dpp/BMP morphogen gradient into an inverse transcriptional gradient. Cell 113: 221-233.

    Article  PubMed  Google Scholar 

  • Newfeld, S.J., Chartoff, E.H., Graff, J.M., Melton, D.A., and Gelbart, W.M., 1996, Mothers against dpp encodes a conserved cytoplasmic protein required in DPP/TGF-β responsive cells. Development 122: 2099-2108.

    PubMed  CAS  Google Scholar 

  • Newfeld, S.J., Mehra, A., Singer, M.A., Wrana, J.L., Attisano, L., and Gelbart, W.M., 1997, Mothers against dpp participates in a DPP/TGF-β responsive serine-threonine kinase signal transduction cascade. Development 124: 3167-3176.

    PubMed  CAS  Google Scholar 

  • Persson, U., Izumi, H., Souchelnytskyi, S., Itoh, S., Grimsby, S., Engström, U., Heldin, C.-H., Funa, K., and ten Dijke, P., 1998, The L45 loop in type I receptors for TGF-β family members is a critical determinant in specifying Smad isoform activation. FEBS Lett 434: 83-87.

    Article  PubMed  CAS  Google Scholar 

  • Podos, S.D., and Ferguson, E.L., 1999, Morphogen gradients: new insights from DPP. Trends Genet 15: 396-402.

    Article  PubMed  CAS  Google Scholar 

  • Pyrowolakis, G., Hartmann, B., Muller, B., Basler, K., and Affolter, M., 2004, A simple molecular complex mediates widespread BMP-induced repression during Drosophila development. Dev Cell 7: 229-240.

    Article  PubMed  CAS  Google Scholar 

  • Raftery, L., and Sutherland, D., 1999, TGF-β family signal transduction in Drosophila: from Mad to Smads. Dev Biol 210: 251-268.

    Article  PubMed  CAS  Google Scholar 

  • Raftery, L.A., and Sutherland, D.J., 2003, Gradients and thresholds: BMP response gradients unveiled in Drosophila embryos. Trends Genet 19: 701-708.

    Article  PubMed  CAS  Google Scholar 

  • Rushlow, C., Colosimo, P.F., Lin, M., Xu, M., and Kirov, N., 2001, Transcriptional regulation of the Drosophila gene zen by competing Smad and Brinker inputs. Genes Dev 15: 340-351.

    Article  PubMed  CAS  Google Scholar 

  • Saller, E., and Bienz, M., 2001, Direct competition between Brinker and Drosophila Mad in Dpp target gene transcription. EMBO Rep 2: 298-305.

    Article  PubMed  CAS  Google Scholar 

  • Saller, E., Kelley, A., and Bienz, M., 2002, The transcriptional repressor Brinker antagonizes Wingless signaling. Genes Dev 16: 1828-1838.

    Article  PubMed  CAS  Google Scholar 

  • Shimmi, O., Umulis, D., Othmer, H., and O’Connor, M.B., 2005, Facilitated transport of a Dpp/Scw heterodimer by Sog/Tsg leads to robust patterning of the Drosophila blastoderm embryo. Cell 120: 873-886.

    Article  PubMed  CAS  Google Scholar 

  • Sivasankaran, R., Vigano, M.A., Muller, B., Affolter, M., and Basler, K., 2000, Direct transcriptional control of the dpp target omb by the DNA binding protein brinker. EMBO J 19: 6162-6172.

    Article  PubMed  CAS  Google Scholar 

  • Song, X., Wong, M.D., Kawase, E., Xi, R., Ding, B.C., McCarthy, J.J., and Xie, T., 2004, Bmp signals from niche cells directly repress transcription of a differentiation-promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary. Development 131: 1353-1364.

    Article  PubMed  CAS  Google Scholar 

  • Sutherland, D.J., Li, M., Liu, X.Q., Stefancsik, R., and Raftery, L.A., 2003, Stepwise formation of a SMAD activity gradient during dorsal-ventral patterning of the Drosophila embryo. Development 130: 5705-5716.

    Article  PubMed  CAS  Google Scholar 

  • Tabata, T., 2001, Genetics of morphogen gradients. Nat Rev Genet 2: 620-630.

    Article  PubMed  CAS  Google Scholar 

  • Tabata, T., and Takei, Y., 2004, Morphogens, their identification and regulation. Development 131: 703-712.

    Article  PubMed  CAS  Google Scholar 

  • Teleman, A.A., and Cohen, S.M., 2000, Dpp gradient formation in the Drosophila wing imaginal disc. Cell 103: 971-980.

    Article  PubMed  CAS  Google Scholar 

  • Tsuneizumi, K., Nakayama, T., Kamoshida, Y., Kornberg, T., Christain, J., and Tabata, T., 1997, Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature 389: 627-630.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Y.C., and Ferguson, E.L., 2005, Spatial bistability of Dpp-receptor interactions during Drosophila dorsal-ventral patterning. Nature 434: 229-234.

    Article  PubMed  CAS  Google Scholar 

  • Wharton, S.J., Basu, S.P., and Ashe, H.L., 2004, Smad affinity can direct distinct readouts of the embryonic extracellular Dpp gradient in Drosophila. Curr Biol 14: 1550-1558.

    Article  PubMed  CAS  Google Scholar 

  • Whitman, M., 1998, Smads and early developmental signaling by the TGFβ superfamily. Genes Dev 12: 2445-2462.

    PubMed  CAS  Google Scholar 

  • Winter, S.E, and Campbell, G., 2004, Repression of Dpp targets in the Drosophila wing by Brinker. Development 131: 6071-6081.

    Article  PubMed  CAS  Google Scholar 

  • Xu, M., Kirov, N., and Rushlow, C., 2005, Peak levels of BMP in the Drosophila embryo control target genes by a feed-forward mechanism. Development 132: 1637-1647.

    Article  PubMed  CAS  Google Scholar 

  • Xu, X., Yin, Z., Hudson, J., Ferguson, E., 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.

    PubMed  CAS  Google Scholar 

  • Yang, M., Nelson, D., Funakoshi, Y., and Padgett, R.W., 2004, Genome-wide microarray analysis of TGFβ signaling in the Drosophila brain. BMC Dev Biol 4: 14.

    Article  PubMed  CAS  Google Scholar 

  • Zheng, X., Wang, J., Haerry, T.E., Wu, A.Y., Martin, J., O’Connor, M.B., Lee, C.H., and Lee, T., 2003, TGF-β signaling activates steroid hormone receptor expression during neuronal remodeling in the Drosophila brain. Cell 112: 303-315.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Cutaneous Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA

    Laurel A. Raftery, Svetlana Korochkina & Jing Cao

Authors
  1. Laurel A. Raftery
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  2. Svetlana Korochkina
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  3. Jing Cao
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Editors and Affiliations

  1. Leiden University Medical Center, Leiden, The Netherlands

    Peter ten Dijke

  2. Ludwig Institute for Cancer Research, Uppsala University, Sweden

    Carl-Henrik Heldin

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© 2006 Springer

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Raftery, L.A., Korochkina, S., Cao, J. (2006). Smads In Drosophila – Interpretation Of Graded Signals In Vivo . In: Dijke, P.t., Heldin, CH. (eds) Smad Signal Transduction. Proteins and Cell Regulation, vol 5. Springer, Dordrecht. https://doi.org/10.1007/1-4020-4709-6_3

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