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Gene Review

dpp  -  decapentaplegic

Drosophila melanogaster

Synonyms: BMP, CG9885, DPP, DPP-C, Dm-DPP, ...
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Disease relevance of dpp


Psychiatry related information on dpp

  • We find that this competitive behavior correlates with, and can be corrected by, the activation of the BMP/Dpp survival signaling pathway [5].

High impact information on dpp

  • We propose that the use of broadly distributed Dpp homodimers and spatially restricted Dpp/Scw heterodimers produces the biphasic signal that is responsible for specifying the two dorsal tissue types [6].
  • Signaling by these ligands is regulated at the extracellular level by the BMP binding proteins Sog and Tsg [6].
  • By employing a method for spatial, temporal, and quantitative control over gene expression, we show that the juxtaposition of cells perceiving different levels of DPP signaling is essential for medial-wing-cell proliferation and can be sufficient to promote the proliferation of cells throughout the wing [7].
  • Conversely, uniform activation of the DPP pathway inhibits cell proliferation in medial wing cells [7].
  • Furthermore, we show that Dpp fails to move across cells mutant for dally and dally-like (dly), two Drosophila glypican members of heparin sulfate proteoglycan (HSPG) [8].

Biological context of dpp

  • Defects in Brk25D receptor function combined with reduced expression of dpp ligand produce mutant phenotypes in the embryo and adult [9].
  • Here we show that the misexpression of sog using the even-skipped stripe-2 enhancer redistributes Dpp signalling in a mutant background in which dpp is expressed throughout the embryo [10].
  • A gene complex acting downstream of dpp in Drosophila wing morphogenesis [11].
  • These findings suggest that cyclic AMP-dependent protein kinase A is a component of the signal transduction pathway through which Hh and Ptc direct localized expression of dpp (or wg) and establish the compartment boundary organizer [12].
  • The divergence in dpp expression is surprising given that all other comparative data on gene expression during insect leg development indicate that the molecular pathways regulating this process are conserved [13].

Anatomical context of dpp

  • These data strongly support the view that the primary phylogenetically conserved function of the Drosophila sog and dpp genes and the homologous Xenopus chordin and BMP-4 genes is to subdivide the primitive embryonic ectoderm into neural versus non-neural domains [14].
  • In addition, abd-A function is required for the expression of wg in the visceral mesoderm posterior to the dpp-expressing cells [15].
  • One consequence of dpp expression is the induction of labial (lab) in the underlying endoderm cells [15].
  • In this report we provide the first direct evidence that sog plays a local role in the lateral region of the blastoderm embryo to oppose Dpp activity in the neuroectoderm [14].
  • Regulatory genes that are required for eye/optic lobe fate, including sine oculis (so) and eyes absent (eya), are turned on in their respective domains by Dpp [16].

Associations of dpp with chemical compounds


Physical interactions of dpp

  • Repression of dpp targets by binding of brinker to mad sites [21].
  • Cell binding and co-immunoprecipitation studies suggest that non-HS-modified Dally retains some ability to bind Dpp or BMP4 [22].
  • Brk25D binds dpp protein and bone morphogenetic protein 2 with high affinity [9].
  • Interestingly, we found that the activity of the enhancer is only stimulated by DPP signaling significantly upon binding of LAB and EXD [23].
  • We have identified a single essential Labial (LAB)/EXD-binding site in a Decapentaplegic (DPP)-responsive enhancer of the homeotic gene lab which drives expression in the developing midgut [23].
  • We show that the transcriptional co-regulator dNAB is a Dpp target in the developing wing that interacts with Brk to eliminate cells with reduced Dpp signaling through the JNK pathway [24].

Enzymatic interactions of dpp

  • We conclude that dSmurf specifically targets phosphorylated MAD to proteasome-dependent degradation and regulates DPP signaling during development [25].
  • Holy Tolloido: Tolloid cleaves SOG/Chordin to free DPP/BMPs [26].

Regulatory relationships of dpp

  • In wild-type embryos, the ability of Dpp to induce expression of dorsal markers including itself (autoactivation) in the neuroectoderm is blocked by sog [14].
  • For target genes to be activated, Dpp signalling must suppress transcription of a repressor encoded by the brinker (brk) gene [27].
  • In early larval development, a short-range Hedgehog signal originating from the posterior compartment of the imaginal wing disc activates expression of genes including decapentaplegic (dpp) in a stripe running along the anterior-posterior compartment boundary [28].
  • We show that restoring expression of eya in loss-of-function dpp mutant backgrounds is sufficient to induce so and dac expression and to rescue eye development [29].
  • However, a direct role for Shn in regulating the transcriptional response to Dpp has not been demonstrated [30].
  • First, Dpp appears to directly enhance the levels of EGF pathway activity within the follicular epithelium [31].
  • Our results demonstrate that, as is the case for patterning, Dpp controls wing growth entirely via repression of the target gene brinker (brk) [32].

Other interactions of dpp

  • Hh is secreted by posterior cells; it acts at short range to induce dorsal anterior cells to secrete Dpp and ventral anterior cells to secrete Wg [33].
  • Both planar transcytosis initiated by Dynamin-mediated endocytosis and extracellular diffusion have been proposed for Dpp movement across cells [8].
  • Local inhibition and long-range enhancement of Dpp signal transduction by Sog [10].
  • We propose that slow-proliferating cells upregulate Brk levels owing to a disadvantage in competing for, or in transducing, the Dpp survival signal [34].
  • Here we show that exd function and Dpp/Wg signalling are antagonistic and divide the leg into two mutually exclusive domains [35].
  • We then determined experimentally in the wing epithelium: (1) the precision of the Dpp concentration gradient; (2) the precision of the Dpp signaling activity profile; and (3) the precision of activation of the Dpp target gene spalt [36].

Analytical, diagnostic and therapeutic context of dpp

  • The patterns of gene expression and the formation of the second midgut constriction in the presence of ectopic dpp are most consistent with a dpp-induced transformation of virtually the entire midgut to cell fates normally seen only in the parasegment (ps)7 and ps8 regions of the midgut [37].
  • Dissection of Dpp-response elements from genes expressed during embryonic mesoderm patterning and midgut morphogenesis provides important insights into the contributions of Smad proteins and tissue-specific transcription factors to spatial regulation of gene expression [38].
  • To examine the relative contribution of the two proteins in the regulation of endogenous Dpp target genes we developed a cell culture assay and show that Shn and Mad act synergistically to induce transcription [30].
  • We also show that the activation of this round of dpp expression is dependent upon prior Dpp signals, the signal transducer Medea, and possibly release from dTCF-mediated repression [39].
  • To test whether this promoter specificity accounts for the regulatory autonomy normally found for the three genes, we used in vivo gene targeting to replace the oaf promoter with a dpp-compatible one in an otherwise normal chromosome [40].


  1. A screen for modifiers of decapentaplegic mutant phenotypes identifies lilliputian, the only member of the Fragile-X/Burkitt's Lymphoma family of transcription factors in Drosophila melanogaster. Su, M.A., Wisotzkey, R.G., Newfeld, S.J. Genetics (2001) [Pubmed]
  2. Evolutionary conservation, developmental expression, and genomic mapping of mammalian Twisted gastrulation. Graf, D., Timmons, P.M., Hitchins, M., Episkopou, V., Moore, G., Ito, T., Fujiyama, A., Fisher, A.G., Merkenschlager, M. Mamm. Genome (2001) [Pubmed]
  3. Influence of melanoma inhibitory activity on transforming growth factor-beta signaling in malignant melanoma. Rothhammer, T., Bosserhoff, A.K. Melanoma Res. (2006) [Pubmed]
  4. Mesangial cell hypertrophy by high glucose is mediated by downregulation of the tumor suppressor PTEN. Mahimainathan, L., Das, F., Venkatesan, B., Choudhury, G.G. Diabetes (2006) [Pubmed]
  5. dMyc transforms cells into super-competitors. Moreno, E., Basler, K. Cell (2004) [Pubmed]
  6. Facilitated transport of a Dpp/Scw heterodimer by Sog/Tsg leads to robust patterning of the Drosophila blastoderm embryo. Shimmi, O., Umulis, D., Othmer, H., O'Connor, M.B. Cell (2005) [Pubmed]
  7. Regulation of cell proliferation by a morphogen gradient. Rogulja, D., Irvine, K.D. Cell (2005) [Pubmed]
  8. Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis but regulated by the glypican members of heparan sulfate proteoglycans. Belenkaya, T.Y., Han, C., Yan, D., Opoka, R.J., Khodoun, M., Liu, H., Lin, X. Cell (2004) [Pubmed]
  9. Identification of two bone morphogenetic protein type I receptors in Drosophila and evidence that Brk25D is a decapentaplegic receptor. Penton, A., Chen, Y., Staehling-Hampton, K., Wrana, J.L., Attisano, L., Szidonya, J., Cassill, J.A., Massagué, J., Hoffmann, F.M. Cell (1994) [Pubmed]
  10. Local inhibition and long-range enhancement of Dpp signal transduction by Sog. Ashe, H.L., Levine, M. Nature (1999) [Pubmed]
  11. A gene complex acting downstream of dpp in Drosophila wing morphogenesis. de Celis, J.F., Barrio, R., Kafatos, F.C. Nature (1996) [Pubmed]
  12. Signal transduction by cAMP-dependent protein kinase A in Drosophila limb patterning. Lepage, T., Cohen, S.M., Diaz-Benjumea, F.J., Parkhurst, S.M. Nature (1995) [Pubmed]
  13. Leg development in flies versus grasshoppers: differences in dpp expression do not lead to differences in the expression of downstream components of the leg patterning pathway. Jockusch, E.L., Nulsen, C., Newfeld, S.J., Nagy, L.M. Development (2000) [Pubmed]
  14. The Drosophila short gastrulation gene prevents Dpp from autoactivating and suppressing neurogenesis in the neuroectoderm. Biehs, B., François, V., Bier, E. Genes Dev. (1996) [Pubmed]
  15. Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos. Reuter, R., Panganiban, G.E., Hoffmann, F.M., Scott, M.P. Development (1990) [Pubmed]
  16. Dpp and Hh signaling in the Drosophila embryonic eye field. Chang, T., Mazotta, J., Dumstrei, K., Dumitrescu, A., Hartenstein, V. Development (2001) [Pubmed]
  17. The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4. Hudson, J.B., Podos, S.D., Keith, K., Simpson, S.L., Ferguson, E.L. Development (1998) [Pubmed]
  18. Receptor serine/threonine kinases implicated in the control of Drosophila body pattern by decapentaplegic. Nellen, D., Affolter, M., Basler, K. Cell (1994) [Pubmed]
  19. Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic. Kim, J., Johnson, K., Chen, H.J., Carroll, S., Laughon, A. Nature (1997) [Pubmed]
  20. Independent roles of the dachshund and eyes absent genes in BMP signaling, axon pathfinding and neuronal specification. Miguel-Aliaga, I., Allan, D.W., Thor, S. Development (2004) [Pubmed]
  21. Repression of dpp targets by binding of brinker to mad sites. Kirkpatrick, H., Johnson, K., Laughon, A. J. Biol. Chem. (2001) [Pubmed]
  22. The function of a Drosophila glypican does not depend entirely on heparan sulfate modification. Kirkpatrick, C.A., Knox, S.M., Staatz, W.D., Fox, B., Lercher, D.M., Selleck, S.B. Dev. Biol. (2006) [Pubmed]
  23. Synergistic activation of a Drosophila enhancer by HOM/EXD and DPP signaling. Grieder, N.C., Marty, T., Ryoo, H.D., Mann, R.S., Affolter, M. EMBO J. (1997) [Pubmed]
  24. The co-regulator dNAB interacts with Brinker to eliminate cells with reduced Dpp signaling. Ziv, O., Suissa, Y., Neuman, H., Dinur, T., Geuking, P., Rhiner, C., Portela, M., Lolo, F., Moreno, E., Gerlitz, O. Development (2009) [Pubmed]
  25. dSmurf selectively degrades decapentaplegic-activated MAD, and its overexpression disrupts imaginal disc development. Liang, Y.Y., Lin, X., Liang, M., Brunicardi, F.C., ten Dijke, P., Chen, Z., Choi, K.W., Feng, X.H. J. Biol. Chem. (2003) [Pubmed]
  26. Holy Tolloido: Tolloid cleaves SOG/Chordin to free DPP/BMPs. Mullins, M.C. Trends Genet. (1998) [Pubmed]
  27. Schnurri mediates Dpp-dependent repression of brinker transcription. Marty, T., Müller, B., Basler, K., Affolter, M. Nat. Cell Biol. (2000) [Pubmed]
  28. The spalt gene links the A/P compartment boundary to a linear adult structure in the Drosophila wing. Sturtevant, M.A., Biehs, B., Marin, E., Bier, E. Development (1997) [Pubmed]
  29. Morphogenetic furrow initiation and progression during eye development in Drosophila: the roles of decapentaplegic, hedgehog and eyes absent. Curtiss, J., Mlodzik, M. Development (2000) [Pubmed]
  30. The zinc finger protein schnurri acts as a Smad partner in mediating the transcriptional response to decapentaplegic. Dai, H., Hogan, C., Gopalakrishnan, B., Torres-Vazquez, J., Nguyen, M., Park, S., Raftery, L.A., Warrior, R., Arora, K. Dev. Biol. (2000) [Pubmed]
  31. The role of Dpp and its inhibitors during eggshell patterning in Drosophila. Shravage, B.V., Altmann, G., Technau, M., Roth, S. Development (2007) [Pubmed]
  32. Growth regulation by Dpp: an essential role for Brinker and a non-essential role for graded signaling levels. Schwank, G., Restrepo, S., Basler, K. Development (2008) [Pubmed]
  33. Complementary and mutually exclusive activities of decapentaplegic and wingless organize axial patterning during Drosophila leg development. Jiang, J., Struhl, G. Cell (1996) [Pubmed]
  34. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Moreno, E., Basler, K., Morata, G. Nature (2002) [Pubmed]
  35. Antagonism between extradenticle function and Hedgehog signalling in the developing limb. González-Crespo, S., Abu-Shaar, M., Torres, M., Martínez-A, C., Mann, R.S., Morata, G. Nature (1998) [Pubmed]
  36. Precision of the Dpp gradient. Bollenbach, T., Pantazis, P., Kicheva, A., Bökel, C., González-Gaitán, M., Jülicher, F. Development (2008) [Pubmed]
  37. Ectopic decapentaplegic in the Drosophila midgut alters the expression of five homeotic genes, dpp, and wingless, causing specific morphological defects. Staehling-Hampton, K., Hoffmann, F.M. Dev. Biol. (1994) [Pubmed]
  38. TGF-beta family signal transduction in Drosophila development: from Mad to Smads. Raftery, L.A., Sutherland, D.J. Dev. Biol. (1999) [Pubmed]
  39. Embryonic enhancers in the dpp disk region regulate a second round of Dpp signaling from the dorsal ectoderm to the mesoderm that represses Zfh-1 expression in a subset of pericardial cells. Johnson, A.N., Bergman, C.M., Kreitman, M., Newfeld, S.J. Dev. Biol. (2003) [Pubmed]
  40. Promoter specificity mediates the independent regulation of neighboring genes. Merli, C., Bergstrom, D.E., Cygan, J.A., Blackman, R.K. Genes Dev. (1996) [Pubmed]
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