Gene Symbol: sty
Description: sprouty
Alias: CG1921, CS3-3, Dmel\CG1921, STY, Spry, Sry, Sty, dSPRY, spry, sprouty, CG1921-PB, CG1921-PC, calcineurin suppressor, chromosome 3, group 3, dSprouty, sty-PB, sty-PC
Species: fruit fly

Top Publications

  1. Hacohen N, Kramer S, Sutherland D, Hiromi Y, Krasnow M. sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways. Cell. 1998;92:253-63 pubmed
    ..In sprouty mutants, the FGF pathway is overactive and ectopic branches are induced on the stalks of primary branches...
  2. Bergmann A, Tugentman M, Shilo B, Steller H. Regulation of cell number by MAPK-dependent control of apoptosis: a mechanism for trophic survival signaling. Dev Cell. 2002;2:159-70 pubmed
    ..Therefore, a direct pathway linking a specific extracellular survival factor with a caspase-based death program has been established. ..
  3. Dutta D, Shaw S, Maqbool T, Pandya H, Vijayraghavan K. Drosophila Heartless acts with Heartbroken/Dof in muscle founder differentiation. PLoS Biol. 2005;3:e337 pubmed
    ..We suggest that the developmental patterns of Heartbroken/Dof and Sprouty result in defining the domain and timing of activation of the Fibroblast growth factor receptor Heartless in ..
  4. Casci T, Vinós J, Freeman M. Sprouty, an intracellular inhibitor of Ras signaling. Cell. 1999;96:655-65 pubmed
    b>Sprouty was identified in a genetic screen as an inhibitor of Drosophila EGF receptor signaling. The Egfr triggers cell recruitment in the eye, and sprouty- eyes have excess photoreceptors, cone cells, and pigment cells...
  5. Kramer S, Okabe M, Hacohen N, Krasnow M, Hiromi Y. Sprouty: a common antagonist of FGF and EGF signaling pathways in Drosophila. Development. 1999;126:2515-25 pubmed
    ..Here we describe the role of Sprouty in eye development...
  6. Freeman M. Feedback control of intercellular signalling in development. Nature. 2000;408:313-9 pubmed
    ..These feedback interactions can impart precision, robustness and versatility to intercellular signals. Feedback failure can cause disease. ..
  7. Bergmann A, Agapite J, McCall K, Steller H. The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling. Cell. 1998;95:331-41 pubmed
    ..These findings define a novel mechanism by which growth factor signaling directly inactivates a critical component of the intrinsic cell death machinery. These studies provide further insights into the function of ras as an oncogene. ..
  8. Jarvis L, Toering S, Simon M, Krasnow M, Smith Bolton R. Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases. Development. 2006;133:1133-42 pubmed
    ..b>Sprouty proteins are tyrosine-phosphorylated RTK feedback inhibitors, but their regulation and mechanism of action are ..
  9. Sen A, Yokokura T, Kankel M, Dimlich D, Manent J, Sanyal S, et al. Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling. J Cell Biol. 2011;192:481-95 pubmed publisher

More Information


  1. Zelzer E, Shilo B. Cell fate choices in Drosophila tracheal morphogenesis. Bioessays. 2000;22:219-26 pubmed
    ..Tracheal cell fate choices are determined by signaling cascades triggered by signals emanating from the tracheal cells, as well as by ligands produced by adjacent tissues. ..
  2. Moon N, Di Stefano L, Dyson N. A gradient of epidermal growth factor receptor signaling determines the sensitivity of rbf1 mutant cells to E2F-dependent apoptosis. Mol Cell Biol. 2006;26:7601-15 pubmed
    ..of rbf1 mutant cells is suppressed by the activation of DER, ras, or raf or by the inactivation of argos, sprouty, or gap1, and inhibition of DER strongly enhances apoptosis in rbf1 mutant discs...
  3. Srahna M, Leyssen M, Choi C, Fradkin L, Noordermeer J, Hassan B. A signaling network for patterning of neuronal connectivity in the Drosophila brain. PLoS Biol. 2006;4:e348 pubmed
    ..JNK activity is necessary and sufficient for axon extension, whereas the antagonistic Wnt and FGF signals act to balance the extension and retraction required for the generation of the precise wiring pattern. ..
  4. Caviglia S, Luschnig S. The ETS domain transcriptional repressor Anterior open inhibits MAP kinase and Wingless signaling to couple tracheal cell fate with branch identity. Development. 2013;140:1240-9 pubmed publisher
    ..The switch from a branching towards an anastomosing tip cell type may have evolved with the acquisition of a main tube that connects separate tracheal primordia to generate a tubular network. ..
  5. Mao Y, Freeman M. Fasciclin 2, the Drosophila orthologue of neural cell-adhesion molecule, inhibits EGF receptor signalling. Development. 2009;136:473-81 pubmed publisher
    ..Our results introduce a new regulatory interaction between an adhesion protein and a Drosophila signalling pathway and highlight the extent to which the EGFR pathway must be regulated at multiple levels. ..
  6. Charroux B, Freeman M, Kerridge S, Baonza A. Atrophin contributes to the negative regulation of epidermal growth factor receptor signaling in Drosophila. Dev Biol. 2006;291:278-90 pubmed
    ..Finally, we have found that expression of pathogenic or normal forms of human Atrophin-1 in the wing promotes wing vein differentiation and acts as dominant negative proteins inhibiting endogenous fly Atrophin activity. ..
  7. Dragojlovic Munther M, Martinez Agosto J. Extracellular matrix-modulated Heartless signaling in Drosophila blood progenitors regulates their differentiation via a Ras/ETS/FOG pathway and target of rapamycin function. Dev Biol. 2013;384:313-30 pubmed publisher
  8. Freeman M. Complexity of EGF receptor signalling revealed in Drosophila. Curr Opin Genet Dev. 1998;8:407-11 pubmed
    ..The integration of signalling pathways into networks is beginning to be understood. ..
  9. Oishi K, Zhang H, Gault W, Wang C, Tan C, Kim I, et al. Phosphatase-defective LEOPARD syndrome mutations in PTPN11 gene have gain-of-function effects during Drosophila development. Hum Mol Genet. 2009;18:193-201 pubmed publisher
  10. Cabernard C, Affolter M. Distinct roles for two receptor tyrosine kinases in epithelial branching morphogenesis in Drosophila. Dev Cell. 2005;9:831-42 pubmed
    ..Ras and the Mapk pathway are also needed for Egf-regulated cell division/survival, but Pointed is dispensable. ..
  11. Zartman J, Cheung L, Niepielko M, Bonini C, Haley B, Yakoby N, et al. Pattern formation by a moving morphogen source. Phys Biol. 2011;8:045003 pubmed publisher
    ..The proposed model of the broad expression pattern can be used as a starting point for the quantitative analysis of a large number of gene expression patterns in Drosophila oogenesis. ..
  12. Kramer S, West S, Hiromi Y. Cell fate control in the Drosophila retina by the orphan receptor seven-up: its role in the decisions mediated by the ras signaling pathway. Development. 1995;121:1361-72 pubmed
    ..However, a decrease in ras signaling results in enhancement of the phenotype caused by the ro-svp transgene. We discuss the relationship between decisions controlled by seven-up and those controlled by ras signaling. ..
  13. Ho Y, Lien M, Lin C, Wei S, Chang L, Hsu J. Echinoid regulates Flamingo endocytosis to control ommatidial rotation in the Drosophila eye. Development. 2010;137:745-54 pubmed publisher
    ..Thus, co-endocytosis of Ed and Fmi provides a link between apicobasal polarity and PCP. ..
  14. Valentine M, Hogan J, Collier S. The Drosophila Chmp1 protein determines wing cell fate through regulation of epidermal growth factor receptor signaling. Dev Dyn. 2014;243:977-87 pubmed publisher
    ..Loss of Chmp1 activity in the Drosophila wing induces a cell fate change from intervein to vein that should provide a useful tool for future studies of ESCRT protein activity. ..
  15. Wang C, Zhao R, Huang P, Yang F, Quan Z, Xu N, et al. APC loss-induced intestinal tumorigenesis in Drosophila: Roles of Ras in Wnt signaling activation and tumor progression. Dev Biol. 2013;378:122-40 pubmed publisher
  16. Bai J, Chiu W, Wang J, Tzeng T, Perrimon N, Hsu J. The cell adhesion molecule Echinoid defines a new pathway that antagonizes the Drosophila EGF receptor signaling pathway. Development. 2001;128:591-601 pubmed
    ..Together, our results support a model whereby ED defines an independent pathway that antagonizes EGFR signaling by regulating the activity, but not the level, of the TTK88 transcriptional repressor. ..
  17. Reich A, Sapir A, Shilo B. Sprouty is a general inhibitor of receptor tyrosine kinase signaling. Development. 1999;126:4139-47 pubmed
    b>Sprouty was originally identified as an inhibitor of Drosophila FGF receptor signaling during tracheal development...
  18. Simakov D, Cheung L, Pismen L, Shvartsman S. EGFR-dependent network interactions that pattern Drosophila eggshell appendages. Development. 2012;139:2814-20 pubmed publisher
    ..The model describes pattern formation in a large number of mutants and points to several unanswered questions related to the dynamic interaction of the EGFR and Notch pathways. ..
  19. Peri F, Bökel C, Roth S. Local Gurken signaling and dynamic MAPK activation during Drosophila oogenesis. Mech Dev. 1999;81:75-88 pubmed
    ..Instead they are specified by secondary signal amplification and refinement processes that integrate the Gurken signal with positive and negative feedback mechanisms generated by target genes of the DER pathway. ..
  20. Sen A, Kuruvilla D, Pinto L, Sarin A, Rodrigues V. Programmed cell death and context dependent activation of the EGF pathway regulate gliogenesis in the Drosophila olfactory system. Mech Dev. 2004;121:65-78 pubmed
    ..These results underscore the importance of developmental context of cell lineages in their responses to non-autonomous signaling in the choice between survival and death. ..
  21. Nicholson S, Gilbert M, Nicolay B, Frolov M, Moberg K. The archipelago tumor suppressor gene limits rb/e2f-regulated apoptosis in developing Drosophila tissues. Curr Biol. 2009;19:1503-10 pubmed publisher
    ..Moreover, the susceptibility of ago mutant cells to succumb to this apoptotic program appears to depend on local variations in extracellular signaling that could thus determine tissue-specific fates of ago mutant cells. ..
  22. Sopko R, Silva E, Clayton L, Gardano L, Barrios Rodiles M, Wrana J, et al. Phosphorylation of the tumor suppressor fat is regulated by its ligand Dachsous and the kinase discs overgrown. Curr Biol. 2009;19:1112-7 pubmed publisher
    ..We propose that Ds regulates Dco-dependent phosphorylation of Fat and Fat-associated proteins to control Fat signaling in growth and PCP. ..
  23. Ahmad S, Busser B, Huang D, Cozart E, Michaud S, Zhu X, et al. Machine learning classification of cell-specific cardiac enhancers uncovers developmental subnetworks regulating progenitor cell division and cell fate specification. Development. 2014;141:878-88 pubmed publisher
  24. Affolter M, Shilo B. Genetic control of branching morphogenesis during Drosophila tracheal development. Curr Opin Cell Biol. 2000;12:731-5 pubmed
    ..More than 30 genes have been identified and ordered into sequential steps controlling branching morphogenesis. These studies have revealed a number of important principles that might be conserved in other systems. ..
  25. Davies J. Do different branching epithelia use a conserved developmental mechanism?. Bioessays. 2002;24:937-48 pubmed
    ..Overall, I come to the tentative conclusion that key mechanisms are highly conserved, at least within vertebrates, but acknowledge that more work needs to be done before the case is proved beyond reasonable doubt. ..
  26. Meier P, Evan G. Dying like flies. Cell. 1998;95:295-8 pubmed
  27. Gafuik C, Steller H. A gain-of-function germline mutation in Drosophila ras1 affects apoptosis and cell fate during development. PLoS ONE. 2011;6:e23535 pubmed publisher
    ..Finally, we used ras1(R68Q) to identify novel genes that interact with Ras and suppress cell death. ..
  28. Rhiner C, Diaz B, Portela M, Poyatos J, Fernández Ruíz I, López Gay J, et al. Persistent competition among stem cells and their daughters in the Drosophila ovary germline niche. Development. 2009;136:995-1006 pubmed publisher
    ..Moreover, competitive interactions among stem cells may be relevant for the successful application of stem cell therapies in humans. ..
  29. Botella J, Kretzschmar D, Kiermayer C, Feldmann P, Hughes D, Schneuwly S. Deregulation of the Egfr/Ras signaling pathway induces age-related brain degeneration in the Drosophila mutant vap. Mol Biol Cell. 2003;14:241-50 pubmed
    ..These results provide the first evidence for a requirement of Egf receptor activity in differentiated adult Drosophila neurons and show that a delicate balance of Ras activity is essential for the survival of adult neurons. ..
  30. Perrimon N, McMahon A. Negative feedback mechanisms and their roles during pattern formation. Cell. 1999;97:13-6 pubmed
  31. Fregoso Lomas M, Hails F, Lachance J, Nilson L. Response to the dorsal anterior gradient of EGFR signaling in Drosophila oogenesis is prepatterned by earlier posterior EGFR activation. Cell Rep. 2013;4:791-802 pubmed publisher
    ..Spatial regulation of the EGFR pathway thus occurs both through localization of the ligand and through localized regulation of the cellular response. ..
  32. Franzdóttir S, Engelen D, Yuva Aydemir Y, Schmidt I, Aho A, Klämbt C. Switch in FGF signalling initiates glial differentiation in the Drosophila eye. Nature. 2009;460:758-61 pubmed publisher
    ..These results disclose an evolutionarily conserved control mechanism of axonal wrapping, indicating that Drosophila might serve as a model to understand glial disorders in humans. ..
  33. Takemura M, Adachi Yamada T. Cell death and selective adhesion reorganize the dorsoventral boundary for zigzag patterning of Drosophila wing margin hairs. Dev Biol. 2011;357:336-46 pubmed publisher
    ..This may be a common mechanism for geometrically ordered repetitive packing of several types of cells in similarly patterned developmental fields such as the mammalian organ of Corti. ..
  34. Iwanami M, Hiromi Y, Okabe M. Cell-type specific utilization of multiple negative feedback loops generates developmental constancy. Genes Cells. 2005;10:743-52 pubmed
    ..Inducing cells secreting EGF express a negative regulator Sprouty (SPRY) that lowers Ras/MAPK signaling activity, and as a consequence reduces the signal-dependent expression of a ..
  35. Strutt H, Strutt D. EGF signaling and ommatidial rotation in the Drosophila eye. Curr Biol. 2003;13:1451-7 pubmed
    ..We now show that two regulators of EGF signaling, argos and sprouty (sty), and a gain-of-function Ras85D allele, interact genetically with fz in ommatidial polarity...
  36. Wong E, Lim J, Low B, Chen Q, Guy G. Evidence for direct interaction between Sprouty and Cbl. J Biol Chem. 2001;276:5866-75 pubmed
    b>Sprouty (SPRY) was first identified in a genetic screen in Drosophila as an antagonist of fibroblast and epidermal growth factor receptors and Sevenless signaling, seemingly by inhibiting the receptor tyrosine kinase (RTK)/Ras/MAPK ..
  37. Taguchi A, Sawamoto K, Okano H. Mutations modulating the Argos-regulated signaling pathway in Drosophila eye development. Genetics. 2000;154:1639-48 pubmed
    ..As a result, new alleles of known genes encoding components of the EGF receptor pathway, such as Star, sprouty, bulge, and clown, were isolated...
  38. Leevers S. What goes up must come down. Nat Cell Biol. 1999;1:E10-1 pubmed
  39. Pallavi S, Kannan R, Shashidhara L. Negative regulation of Egfr/Ras pathway by Ultrabithorax during haltere development in Drosophila. Dev Biol. 2006;296:340-52 pubmed
    ..These results and other recent findings suggest that homeotic genes may regulate cell fate determination by directly regulating few steps at the top of the hierarchy of selected signal transduction pathways. ..
  40. Sasaki A, Taketomi T, Wakioka T, Kato R, Yoshimura A. Identification of a dominant negative mutant of Sprouty that potentiates fibroblast growth factor- but not epidermal growth factor-induced ERK activation. J Biol Chem. 2001;276:36804-8 pubmed
    ..These mutants reverted the suppressive effect of both Sprouty2 and Sprouty4 but not that of RasGAP or SPRED (Sprouty-related EVH1 domain-containing protein), another Sprouty-related Ras suppressor...
  41. Abrell S, Carrera P, Jackle H. A modifier screen of ectopic Krüppel activity identifies autosomal Drosophila chromosomal sites and genes required for normal eye development. Chromosoma. 2000;109:334-42 pubmed
    ..Owing to the bias of the screening system applied, these modifier genes will be expressed and are likely to be required during Drosophila wild-type eye development. ..
  42. Forbes A, Lehmann R. Cell migration in Drosophila. Curr Opin Genet Dev. 1999;9:473-8 pubmed
    ..In the female germline, the migratory path of border cells is directed by the homophilic adhesion molecule E cadherin. ..
  43. Hogan B, Yingling J. Epithelial/mesenchymal interactions and branching morphogenesis of the lung. Curr Opin Genet Dev. 1998;8:481-6 pubmed
    ..Although there are obvious differences in the complexity of these branched organs, many of the underlying mechanisms and genes regulating their development appear to have been evolutionarily conserved. ..
  44. Dollar G, Gombos R, Barnett A, Sanchez Hernandez D, Maung S, Mihály J, et al. Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila. Genetics. 2016;202:1135-51 pubmed publisher
    ..It furthermore highlights the importance and complexity of formin-dependent cytoskeletal regulation in multiple organs and developmental contexts. ..
  45. Duchek P, Somogyi K, Jekely G, Beccari S, Rørth P. Guidance of cell migration by the Drosophila PDGF/VEGF receptor. Cell. 2001;107:17-26 pubmed
    ..Intriguingly, the guidance function of PVR is largely redundant with that of EGFR. We present evidence implicating Rac and the Rac activator Mbc/DOCK180/CED-5 as mediators of the guidance signal. ..
  46. Sieglitz F, Matzat T, Yuva Aydemir Y, Yuva Adyemir Y, Neuert H, Altenhein B, et al. Antagonistic feedback loops involving Rau and Sprouty in the Drosophila eye control neuronal and glial differentiation. Sci Signal. 2013;6:ra96 pubmed publisher
    ..domain-containing protein Rau that sustained Ras activity and counteracted the negative feedback loop mediated by Sprouty. Rau has two RA domains that together showed a binding preference for GTP (guanosine 5'-triphosphate)-loaded (..
  47. Metzger R, Krasnow M. Genetic control of branching morphogenesis. Science. 1999;284:1635-9 pubmed
    ..The reiterative use of a signaling pathway by both insects and mammals suggests a general scheme for patterning branching morphogenesis. ..
  48. Peterson S, Krasnow M. Subcellular trafficking of FGF controls tracheal invasion of Drosophila flight muscle. Cell. 2015;160:313-23 pubmed publisher
    ..We propose that tracheal invasion is controlled by an AP-1-dependent switch in FGF trafficking. Thus, subcellular targeting of a chemoattractant can direct outgrowth to specific domains, including inside the cell. ..
  49. Kim H, Bar Sagi D. Modulation of signalling by Sprouty: a developing story. Nat Rev Mol Cell Biol. 2004;5:441-50 pubmed
  50. Boisclair Lachance J, Fregoso Lomas M, Eleiche A, Bouchard Kerr P, Nilson L. Graded Egfr activity patterns the Drosophila eggshell independently of autocrine feedback. Development. 2009;136:2893-902 pubmed publisher
  51. Firth L, Baker N. EGF receptor signaling: a prickly proposition. Curr Biol. 2003;13:R773-4 pubmed
  52. Gao F, Brenman J, Jan L, Jan Y. Genes regulating dendritic outgrowth, branching, and routing in Drosophila. Genes Dev. 1999;13:2549-61 pubmed
    ..These findings begin to reveal the molecular mechanisms controlling dendritic morphogenesis. ..
  53. Zettl M, Adrain C, Strisovsky K, Lastun V, Freeman M. Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling. Cell. 2011;145:79-91 pubmed publisher
    ..Inactive cognates of enzymes are common, but their functions are mostly unclear; our data indicate that pseudoenzymes can readily evolve into regulatory proteins, suggesting that this may be a significant evolutionary mechanism. ..
  54. Herranz H, Hong X, Cohen S. Mutual repression by bantam miRNA and Capicua links the EGFR/MAPK and Hippo pathways in growth control. Curr Biol. 2012;22:651-7 pubmed publisher
    ..Feedback regulation by bantam on Capicua provides a means to link signal propagation by the EGFR pathway to activity of the Hippo pathway and may play an important role in integration of these two pathways in growth control. ..
  55. Bogdan S, Klämbt C. Epidermal growth factor receptor signaling. Curr Biol. 2001;11:R292-5 pubmed
  56. Lee T, Yu L, Wolf M, Rockman H. Galactokinase is a novel modifier of calcineurin-induced cardiomyopathy in Drosophila. Genetics. 2014;198:591-603 pubmed publisher
  57. Brown K, Baonza A, Freeman M. Epithelial cell adhesion in the developing Drosophila retina is regulated by Atonal and the EGF receptor pathway. Dev Biol. 2006;300:710-21 pubmed
    ..These observations define a new function for EGFR signalling in eye development and illustrate a mechanism for the control of epithelial morphology by developmental signals. ..
  58. Depraetere V. Wingless and naked. Nat Cell Biol. 2000;2:E40 pubmed
  59. Llimargas M. The Notch pathway helps to pattern the tips of the Drosophila tracheal branches by selecting cell fates. Development. 1999;126:2355-64 pubmed
    ..Both the localised expression and the mutant phenotypes of Delta, a known ligand for Notch, suggest that Delta may activate Notch to specify cell fates at the tips of the developing tracheal branches. ..
  60. Samakovlis C, Hacohen N, Manning G, Sutherland D, Guillemin K, Krasnow M. Development of the Drosophila tracheal system occurs by a series of morphologically distinct but genetically coupled branching events. Development. 1996;122:1395-407 pubmed
    ..The combined morphological, marker expression and genetic data support a model in which successive branching events are mechanistically and genetically distinct but coupled through the action of a tracheal gene regulatory hierarchy. ..
  61. Zartman J, Kanodia J, Cheung L, Shvartsman S. Feedback control of the EGFR signaling gradient: superposition of domain-splitting events in Drosophila oogenesis. Development. 2009;136:2903-11 pubmed publisher
    ..Two negative-feedback loops provided by the intracellular inhibitors of EGFR signaling, Kekkon-1 and Sprouty, control the number and position of Broad-expressing cells and in this way influence eggshell morphology...
  62. Lim J, Wong E, Ong S, Yusoff P, Low B, Guy G. Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain. J Biol Chem. 2000;275:32837-45 pubmed
    b>Sprouty (Spry) was first identified in a genetic screen in Drosophila to be an antagonist of fibroblast growth factor and epidermal growth factor (EGF) signaling, seemingly by inhibiting the Ras/MAP kinase pathway...