Skip to main content

Advertisement

SpringerLink
Log in

Regulatory mechanisms of EGFR signalling during Drosophila eye development

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

EGFR signalling is a well-conserved signalling pathway playing major roles during development and cancers. This review explores what studying the EGFR pathway during Drosophila eye development has taught us in terms of the diversity of its regulatory mechanisms. This model system has allowed the identification of numerous positive and negative regulators acting at specific time and place, thus participating to the tight control of signalling. EGFR signalling regulation is achieved by a variety of mechanisms, including the control of ligand processing, the availability of the receptor itself and the transduction of the cascade in the cytoplasm. Ultimately, the transcriptional responses contribute to the establishment of positive and negative feedback loops. The combination of these multiple mechanisms employed to regulate the EGFR pathway leads to specific cellular outcomes involved in functions as diverse as the acquisition of cell fate, proliferation, survival, adherens junction remodelling and morphogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Livneh E, Glazer L, Segal D et al (1985) The Drosophila EGF receptor gene homolog: conservation of both hormone binding and kinase domains. Cell 40:599–607

    Article  CAS  PubMed  Google Scholar 

  2. Singh B, Coffey RJ (2014) Trafficking of epidermal growth factor receptor ligands in polarized epithelial cells. Annu Rev Physiol 76:275–300. doi:10.1146/annurev-physiol-021113-170406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nicholson RI, Gee JM, Harper ME (2001) EGFR and cancer prognosis. Eur J Cancer 37(Suppl 4):S9–15

    Article  CAS  PubMed  Google Scholar 

  4. Uberall I, Kolár Z, Trojanec R et al (2008) The status and role of ErbB receptors in human cancer. Exp Mol Pathol 84:79–89. doi:10.1016/j.yexmp.2007.12.002

    Article  CAS  PubMed  Google Scholar 

  5. Gomez GG, Wykosky J, Zanca C et al (2013) Therapeutic resistance in cancer: microRNA regulation of EGFR signaling networks. Cancer Biol Med 10:192–205. doi:10.7497/j.issn.2095-3941.2013.04.003

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Sasaki T, Hiroki K, Yamashita Y (2013) The role of epidermal growth factor receptor in cancer metastasis and microenvironment. Biomed Res Int. doi:10.1155/2013/546318

    PubMed  PubMed Central  Google Scholar 

  7. Shilo BZ (2003) Signaling by the Drosophila epidermal growth factor receptor pathway during development. Exp Cell Res 284:140–149

    Article  CAS  PubMed  Google Scholar 

  8. Rutledge BJ, Zhang K, Bier E et al (1992) The Drosophila spitz gene encodes a putative EGF-like growth factor involved in dorsal–ventral axis formation and neurogenesis. Genes Dev 6:1503–1517

    Article  CAS  PubMed  Google Scholar 

  9. Reich A, Shilo B-Z (2002) Keren, a new ligand of the Drosophila epidermal growth factor receptor, undergoes two modes of cleavage. EMBO J 21:4287–4296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Schnepp B, Grumbling G, Donaldson T, Simcox A (1996) Vein is a novel component in the Drosophila epidermal growth factor receptor pathway with similarity to the neuregulins. Genes Dev 10:2302–2313

    Article  CAS  PubMed  Google Scholar 

  11. González-Reyes A, Elliott H, St Johnston D (1995) Polarization of both major body axes in Drosophila by gurken-torpedo signalling. Nature 375:654–658. doi:10.1038/375654a0

    Article  PubMed  Google Scholar 

  12. Olivier JP, Raabe T, Henkemeyer M et al (1993) A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. Cell 73:179–191

    Article  CAS  PubMed  Google Scholar 

  13. Lai KMV, Olivier JP, Gish GD et al (1995) A Drosophila shc gene product is implicated in signaling by the DER receptor tyrosine kinase. Mol Cell Biol 15:4810–4818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bonfini L, Karlovich CA, Dasgupta C, Banerjee U (1992) The Son of sevenless gene product: a putative activator of Ras. Science 255:603–606

    Article  CAS  PubMed  Google Scholar 

  15. Simon MA, Bowtell DDL, Dodson GS et al (1991) Ras1 and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. Cell 67:701–716

    Article  CAS  PubMed  Google Scholar 

  16. Bogdan S, Klämbt C (2001) Epidermal growth factor receptor signaling. Curr Biol 11:R292–R295

    Article  CAS  PubMed  Google Scholar 

  17. Shilo B-Z (2014) The regulation and functions of MAPK pathways in Drosophila. Methods 68:151–159. doi:10.1016/j.ymeth.2014.01.020

    Article  CAS  PubMed  Google Scholar 

  18. Ambrosio L, Mahowald AP, Perrimon N (1989) Requirement of the Drosophila raf homologue for torso function. Nature 342:288–291

    Article  CAS  PubMed  Google Scholar 

  19. Tsuda L, Inoue YH, Yoo MA et al (1993) A protein kinase similar to MAP kinase activator acts downstream of the raf kinase in Drosophila. Cell 72:407–414

    Article  CAS  PubMed  Google Scholar 

  20. Biggs WH, Zipursky SL (1992) Primary structure, expression, and signal-dependent tyrosine phosphorylation of a Drosophila homolog of extracellular signal-regulated kinase. Proc Natl Acad Sci USA 89:6295–6299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. O’Neill EM, Rebay I, Tjian R, Rubin GM (1994) The activities of two Ets-related transcription factors required for Drosophila eye development are modulated by the Ras/MAPK pathway. Cell 78:137–147

    Article  PubMed  Google Scholar 

  22. Huang PH, Xu AM, White FM (2009) Oncogenic EGFR signaling networks in glioma. Sci Signal 2:re6. doi:10.1126/scisignal.287re6

    PubMed  Google Scholar 

  23. Cagan R (2009) Principles of Drosophila eye differentiation. Curr Top Dev Biol 89:115–135. doi:10.1016/S0070-2153(09)89005-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kumar JP (2012) Building an ommatidium one cell at a time. Dev Dyn 241:136–149. doi:10.1002/dvdy.23707

    Article  PubMed  PubMed Central  Google Scholar 

  25. Treisman JE (2013) Retinal differentiation in Drosophila. Wiley Interdiscip Rev Dev Biol 2:545–557. doi:10.1002/wdev.100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Baker NE, Rubin GM (1992) Ellipse mutations in the Drosophila homologue of the EGF receptor affect pattern formation, cell division, and cell death in eye imaginal discs. Dev Biol 150:381–396

    Article  CAS  PubMed  Google Scholar 

  27. Domínguez M, Wasserman JD, Freeman M (1998) Multiple functions of the EGF receptor in Drosophila eye development. Curr Biol 8:1039–1048

    Article  PubMed  Google Scholar 

  28. Freeman M (1996) Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. Cell 87:651–660

    Article  CAS  PubMed  Google Scholar 

  29. Freeman M (1997) Cell determination strategies in the Drosophila eye. Development 124:261–270

    CAS  PubMed  Google Scholar 

  30. Freeman M (1998) Complexity of EGF receptor signalling revealed in Drosophila. Curr Opin Genet Dev 8:407–411

    Article  CAS  PubMed  Google Scholar 

  31. Vieira AV, Lamaze C, Schmid SL (1996) Control of EGF receptor signaling by clathrin-mediated endocytosis. Science 274:2086–2089

    Article  CAS  PubMed  Google Scholar 

  32. Legent K, Steinhauer J, Richard M, Treisman JE (2012) A screen for X-linked mutations affecting Drosophila photoreceptor differentiation identifies casein kinase 1α as an essential negative regulator of wingless signaling. Genetics 190:601–616. doi:10.1534/genetics.111.133827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Legent K, Liu HH, Treisman JE (2015) Drosophila Vps4 promotes epidermal growth factor receptor signaling independently of its role in receptor degradation. Development 142:1480–1491. doi:10.1242/dev.117960

    Article  CAS  PubMed  Google Scholar 

  34. Pai LM, Barcelo G, Schüpbach T (2000) D-cbl, a negative regulator of the Egfr pathway, is required for dorsoventral patterning in Drosophila oogenesis. Cell 103:51–61

    Article  CAS  PubMed  Google Scholar 

  35. Swaminathan G, Tsygankov AY (2006) The Cbl family proteins: ring leaders in regulation of cell signaling. J Cell Physiol 209:21–43. doi:10.1002/jcp.20694

    Article  CAS  PubMed  Google Scholar 

  36. Wang Y, Chen Z, Bergmann A (2010) Regulation of EGFR and Notch signaling by distinct isoforms of D-cbl during Drosophila development. Dev Biol 342:1–10. doi:10.1016/j.ydbio.2010.03.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ho Y-H, Lien M-T, Lin C-M et al (2010) Echinoid regulates Flamingo endocytosis to control ommatidial rotation in the Drosophila eye. Development 137:745–754. doi:10.1242/dev.040238

    Article  CAS  PubMed  Google Scholar 

  38. Miura GI, Roignant J-Y, Wassef M, Treisman JE (2008) Myopic acts in the endocytic pathway to enhance signaling by the Drosophila EGF receptor. Development 135:1913–1922. doi:10.1242/dev.017202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Brown KE, Kerr M, Freeman M (2007) The EGFR ligands Spitz and Keren act cooperatively in the Drosophila eye. Dev Biol 307:105–113. doi:10.1016/j.ydbio.2007.04.025

    Article  CAS  PubMed  Google Scholar 

  40. Yang L, Baker NE (2003) Cell cycle withdrawal, progression, and cell survival regulation by EGFR and its effectors in the differentiating Drosophila eye. Dev Cell 4:359–369

    Article  CAS  PubMed  Google Scholar 

  41. Schweitzer R, Shaharabany M, Seger R, Shilo BZ (1995) Secreted Spitz triggers the DER signaling pathway and is a limiting component in embryonic ventral ectoderm determination. Genes Dev 9:1518–1529

    Article  CAS  PubMed  Google Scholar 

  42. Urban S, Lee JR, Freeman M (2001) Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases. Cell 107:173–182

    Article  CAS  PubMed  Google Scholar 

  43. Miura GI, Buglino J, Alvarado D et al (2006) Palmitoylation of the EGFR Ligand Spitz by Rasp Increases Spitz Activity by Restricting Its Diffusion. Dev Cell 10:167–176. doi:10.1016/j.devcel.2005.11.017

    Article  CAS  PubMed  Google Scholar 

  44. Lee JR, Urban S, Garvey CF, Freeman M (2001) Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. Cell 107:161–171

    Article  CAS  PubMed  Google Scholar 

  45. Zettl M, Adrain C, Strisovsky K et al (2011) Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling. Cell 145:79–91. doi:10.1016/j.cell.2011.02.047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kolodkin AL, Pickup AT, Lin DM et al (1994) Characterization of Star and its interactions with sevenless and EGF receptor during photoreceptor cell development in Drosophila. Development 120:1731–1745

    CAS  PubMed  Google Scholar 

  47. Bier E, Jan LY, Jan YN (1990) Rhomboid, a gene required for dorsoventral axis establishment and peripheral nervous system development in Drosophila melanogaster. Genes Dev 4:190–203

    Article  CAS  PubMed  Google Scholar 

  48. Freeman M (2014) The rhomboid-like superfamily: molecular mechanisms and biological roles. Annu Rev Cell Dev Biol 30:235–254. doi:10.1146/annurev-cellbio-100913-012944

    Article  CAS  PubMed  Google Scholar 

  49. Freeman M, Kimmel BE, Rubin GM (1992) Identifying targets of the rough homeobox gene of Drosophila: evidence that rhomboid functions in eye development. Development 116:335–346

    CAS  PubMed  Google Scholar 

  50. Wasserman JD, Urban S, Freeman M (2000) A family of rhomboid-like genes: Drosophila rhomboid-1 and roughoid/rhomboid-3 cooperate to activate EGF receptor signaling. Genes Dev 14:1651–1663

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Mayer U, Nüsslein-Volhard C (1988) A group of genes required for pattern formation in the ventral ectoderm of the Drosophila embryo. Genes Dev 2:1496–1511

    Article  CAS  PubMed  Google Scholar 

  52. Urban S, Lee JR, Freeman M (2002) A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF ligands. EMBO J 21:4277–4286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Tsruya R, Wojtalla A, Carmon S et al (2007) Rhomboid cleaves Star to regulate the levels of secreted Spitz. EMBO J 26:1211–1220. doi:10.1038/sj.emboj.7601581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Yogev S, Schejter ED, Shilo B-Z (2008) Drosophila EGFR signalling is modulated by differential compartmentalization of Rhomboid intramembrane proteases. EMBO J 27:1219–1230. doi:10.1038/emboj.2008.58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Steinhauer J, Liu HH, Miller E, Treisman JE (2013) Trafficking of the EGFR ligand Spitz regulates its signaling activity in polarized tissues. J Cell Sci 126:4469–4478. doi:10.1242/jcs.131169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gabay L, Seger R, Shilo BZ (1997) In situ activation pattern of Drosophila EGF receptor pathway during development. Science 277:1103–1106

    Article  CAS  PubMed  Google Scholar 

  57. Roignant J-Y, Treisman JE (2010) Exon junction complex subunits are required to splice Drosophila MAP kinase, a large heterochromatic gene. Cell 143:238–250. doi:10.1016/j.cell.2010.09.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Therrien M, Chang HC, Solomon NM et al (1995) KSR, a novel protein kinase required for RAS signal transduction. Cell 83:879–888

    Article  CAS  PubMed  Google Scholar 

  59. Kolch W (2005) Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat Rev Mol Cell Biol 6:827–837. doi:10.1038/nrm1743

    Article  CAS  PubMed  Google Scholar 

  60. Rajakulendran T, Sahmi M, Lefrançois M et al (2009) A dimerization-dependent mechanism drives RAF catalytic activation. Nature 461:542–545. doi:10.1038/nature08314

    Article  CAS  PubMed  Google Scholar 

  61. Therrien M, Wong AM, Rubin GM (1998) CNK, a RAF-binding multidomain protein required for RAS signaling. Cell 95:343–353. doi:10.1016/S0092-8674(00)81766-3

    Article  CAS  PubMed  Google Scholar 

  62. Douziech M, Roy F, Laberge G et al (2003) Bimodal regulation of RAF by CNK in Drosophila. EMBO J 22:5068–5078. doi:10.1093/emboj/cdg506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Douziech M, Sahmi M, Laberge G, Therrien M (2006) A KSR/CNK complex mediated by HYP, a novel SAM domain-containing protein, regulates RAS-dependent RAF activation in Drosophila. Genes Dev 20:807–819. doi:10.1101/gad.1390406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Roignant J-Y, Hamel S, Janody F, Treisman JE (2006) The novel SAM domain protein Aveugle is required for Raf activation in the Drosophila EGF receptor signaling pathway. Genes Dev 20:795–806. doi:10.1101/gad.1390506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Rajakulendran T, Sahmi M, Kurinov I et al (2008) CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling. Proc Natl Acad Sci USA 105:2836–2841. doi:10.1073/pnas.0709705105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hahn I, Fuss B, Peters A et al (2013) The Drosophila Arf GEF Steppke controls MAPK activation in EGFR signaling. J Cell Sci 126:2470–2479. doi:10.1242/jcs.120964

    Article  CAS  PubMed  Google Scholar 

  67. Johnson Hamlet MR, Perkins LA (2001) Analysis of corkscrew signaling in the Drosophila epidermal growth factor receptor pathway during myogenesis. Genetics 159:1073–1087

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Perkins LA, Larsen I, Perrimon N (1992) corkscrew encodes a putative protein tyrosine phosphatase that functions to transduce the terminal signal from the receptor tyrosine kinase torso. Cell 70:225–236

    Article  CAS  PubMed  Google Scholar 

  69. Jarvis LA, Toering SJ, Simon MA et al (2006) Sprouty proteins are in vivo targets of Corkscrew/SHP-2 tyrosine phosphatases. Development 133:1133–1142. doi:10.1242/dev.02255

    Article  CAS  PubMed  Google Scholar 

  70. Freeman M, Klämbt C, Goodman CS, Rubin GM (1992) The argos gene encodes a diffusible factor that regulates cell fate decisions in the Drosophila eye. Cell 69:963–975

    Article  CAS  PubMed  Google Scholar 

  71. Freeman M (1994) Misexpression of the Drosophila argos gene, a secreted regulator of cell determination. Development 120:2297–2304

    CAS  PubMed  Google Scholar 

  72. Jin MH, Sawamoto K, Ito M, Okano H (2000) The interaction between the Drosophila secreted protein argos and the epidermal growth factor receptor inhibits dimerization of the receptor and binding of secreted spitz to the receptor. Mol Cell Biol 20:2098–2107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Vinós J, Freeman M (2000) Evidence that Argos is an antagonistic ligand of the EGF receptor. Oncogene 19:3560–3562. doi:10.1038/sj.onc.1203702

    Article  PubMed  Google Scholar 

  74. Klein DE, Nappi VM, Reeves GT et al (2004) Argos inhibits epidermal growth factor receptor signalling by ligand sequestration. Nature 430:1040–1044. doi:10.1038/nature02840

    Article  CAS  PubMed  Google Scholar 

  75. Shilo B-Z (2005) Regulating the dynamics of EGF receptor signaling in space and time. Development 132:4017–4027. doi:10.1242/dev.02006

    Article  CAS  PubMed  Google Scholar 

  76. Ghiglione C, Amundadottir L, Andresdottir M et al (2003) Mechanism of inhibition of the Drosophila and mammalian EGF receptors by the transmembrane protein Kekkon 1. Development 130:4483–4493

    Article  CAS  PubMed  Google Scholar 

  77. Bai J, Chiu W, Wang J et al (2001) The cell adhesion molecule Echinoid defines a new pathway that antagonizes the Drosophila EGF receptor signaling pathway. Development 128:591–601

    CAS  PubMed  Google Scholar 

  78. Spencer SA, Cagan RL (2003) Echinoid is essential for regulation of Egfr signaling and R8 formation during Drosophila eye development. Development 130:3725–3733

    Article  CAS  PubMed  Google Scholar 

  79. Islam R, Wei S-Y, Chiu W-H et al (2003) Neuroglian activates Echinoid to antagonize the Drosophila EGF receptor signaling pathway. Development 130:2051–2059

    Article  CAS  PubMed  Google Scholar 

  80. Mao Y, Freeman M (2009) Fasciclin 2, the Drosophila orthologue of neural cell-adhesion molecule, inhibits EGF receptor signalling. Development 136:473–481. doi:10.1242/dev.026054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Casci T, Vinós J, Freeman M (1999) Sprouty, an intracellular inhibitor of Ras signaling. Cell 96:655–665. doi:10.1016/S0092-8674(00)80576-0

    Article  CAS  PubMed  Google Scholar 

  82. Kramer S, Okabe M, Hacohen N et al (1999) Sprouty: a common antagonist of FGF and EGF signaling pathways in Drosophila. Development 126:2515–2525

    CAS  PubMed  Google Scholar 

  83. Gaul U, Mardon G, Rubin GM (1992) A putative Ras GTPase activating protein acts as a negative regulator of signaling by the Sevenless receptor tyrosine kinase. Cell 68:1007–1019

    Article  CAS  PubMed  Google Scholar 

  84. Kim HJ, Taylor LJ, Bar-Sagi D (2007) Spatial regulation of EGFR signaling by Sprouty2. Curr Biol 17:455–461. doi:10.1016/j.cub.2007.01.059

    Article  CAS  PubMed  Google Scholar 

  85. Bruinsma SP, Cagan RL, Baranski TJ (2007) Chimaerin and Rac regulate cell number, adherens junctions, and ERK MAP kinase signaling in the Drosophila eye. Proc Natl Acad Sci USA 104:7098–7103. doi:10.1073/pnas.0701686104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Sarkar A, Parikh N, Hearn SA et al (2007) Antagonistic roles of Rac and Rho in organizing the germ cell microenvironment. Curr Biol 17:1253–1258. doi:10.1016/j.cub.2007.06.048

    Article  CAS  PubMed  Google Scholar 

  87. Tamás P, Solti Z, Bauer P et al (2003) Mechanism of epidermal growth factor regulation of Vav2, a guanine nucleotide exchange factor for Rac. J Biol Chem 278:5163–5171. doi:10.1074/jbc.M207555200

    Article  PubMed  CAS  Google Scholar 

  88. Martín-Bermudo M-D, Bardet P-L, Bellaïche Y, Malartre M (2015) The vav oncogene antagonises EGFR signalling and regulates adherens junction dynamics during Drosophila eye development. Development 142:1492–1501. doi:10.1242/dev.110585

    Article  PubMed  CAS  Google Scholar 

  89. Lazer G, Katzav S (2011) Guanine nucleotide exchange factors for RhoGTPases: good therapeutic targets for cancer therapy? Cell Signal 23:969–979. doi:10.1016/j.cellsig.2010.10.022

    Article  CAS  PubMed  Google Scholar 

  90. Schlesinger A, Kiger A, Perrimon N, Shilo B-Z (2004) Small wing PLCgamma is required for ER retention of cleaved Spitz during eye development in Drosophila. Dev Cell 7:535–545. doi:10.1016/j.devcel.2004.09.001

    Article  CAS  PubMed  Google Scholar 

  91. Yogev S, Schejter ED, Shilo B-Z (2010) Polarized secretion of Drosophila EGFR ligand from photoreceptor neurons is controlled by ER localization of the ligand-processing machinery. PLoS Biol. doi:10.1371/journal.pbio.1000505

    Google Scholar 

  92. Tsruya R, Schlesinger A, Reich A et al (2002) Intracellular trafficking by Star regulates cleavage of the Drosophila EGF receptor ligand Spitz. Genes Dev 16:222–234. doi:10.1101/gad.214202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Rusconi JC, Fink JL, Cagan R (2004) klumpfuss regulates cell death in the Drosophila retina. Mech Dev 121:537–546. doi:10.1016/j.mod.2004.04.008

    Article  CAS  PubMed  Google Scholar 

  94. Wildonger J, Sosinsky A, Honig B, Mann RS (2005) Lozenge directly activates argos and klumpfuss to regulate programmed cell death. Genes Dev 19:1034–1039. doi:10.1101/gad.1298105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Protzer CE, Wech I, Nagel AC (2008) Hairless induces cell death by downregulation of EGFR signalling activity. J Cell Sci 121:3167–3176. doi:10.1242/jcs.035014

    Article  CAS  PubMed  Google Scholar 

  96. Kumar JP, Hsiung F, Powers MA, Moses K (2003) Nuclear translocation of activated MAP kinase is developmentally regulated in the developing Drosophila eye. Development 130:3703–3714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Rebay I, Rubin GM (1995) Yan functions as a general inhibitor of differentiation and is negatively regulated by activation of the Ras1/MAPK pathway. Cell 81:857–866

    Article  CAS  PubMed  Google Scholar 

  98. Shwartz A, Yogev S, Schejter ED, Shilo B-Z (2013) Sequential activation of ETS proteins provides a sustained transcriptional response to EGFR signaling. Development 140:2746–2754. doi:10.1242/dev.093138

    Article  CAS  PubMed  Google Scholar 

  99. Astigarraga S, Grossman R, Díaz-Delfín J et al (2007) A MAPK docking site is critical for downregulation of Capicua by Torso and EGFR RTK signaling. EMBO J 26:668–677. doi:10.1038/sj.emboj.7601532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Tseng A-SK, Tapon N, Kanda H et al (2007) Capicua regulates cell proliferation downstream of the receptor tyrosine kinase/Ras signaling pathway. Curr Biol 17:728–733. doi:10.1016/j.cub.2007.03.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Anderson J, Bhandari R, Kumar JP (2005) A genetic screen identifies putative targets and binding partners of CREB-binding protein in the developing Drosophila eye. Genetics 171:1655–1672. doi:10.1534/genetics.105.045450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Ruohola-Baker H, Grell E, Chou T-B et al (1993) Spatially localized rhomboid is required for establishment of the dorsal–ventral axis in Drosophila oogenesis. Cell 73:953–965. doi:10.1016/0092-8674(93)90273-S

    Article  CAS  PubMed  Google Scholar 

  103. Golembo M, Schweitzer R, Freeman M, Shilo BZ (1996) Argos transcription is induced by the Drosophila EGF receptor pathway to form an inhibitory feedback loop. Development 122:223–230

    CAS  PubMed  Google Scholar 

  104. Wasserman JD, Freeman M (1998) An autoregulatory cascade of EGF receptor signaling patterns the Drosophila egg. Cell 95:355–364

    Article  CAS  PubMed  Google Scholar 

  105. Ghiglione C, Carraway KL 3rd, Amundadottir LT et al (1999) The transmembrane molecule kekkon 1 acts in a feedback loop to negatively regulate the activity of the Drosophila EGF receptor during oogenesis. Cell 96:847–856

    Article  CAS  PubMed  Google Scholar 

  106. Kumar JP, Moses K (2001) EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification. Cell 104:687–697

    Article  CAS  PubMed  Google Scholar 

  107. Xu T, Rubin GM (1993) Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117:1223–1237

    CAS  PubMed  Google Scholar 

  108. Baker NE, Yu SY (2001) The EGF receptor defines domains of cell cycle progression and survival to regulate cell number in the developing Drosophila eye. Cell 104:699–708

    Article  CAS  PubMed  Google Scholar 

  109. Firth LC, Baker NE (2005) Extracellular signals responsible for spatially regulated proliferation in the differentiating Drosophila eye. Dev Cell 8:541–551. doi:10.1016/j.devcel.2005.01.017

    Article  CAS  PubMed  Google Scholar 

  110. Baonza A, Murawsky CM, Travers AA, Freeman M (2002) Pointed and Tramtrack69 establish an EGFR-dependent transcriptional switch to regulate mitosis. Nat Cell Biol 4:976–980. doi:10.1038/ncb887

    Article  CAS  PubMed  Google Scholar 

  111. Kumar JP, Moses K (2001) The EGF receptor and notch signaling pathways control the initiation of the morphogenetic furrow during Drosophila eye development. Development 128:2689–2697

    CAS  PubMed  Google Scholar 

  112. Kumar JP, Tio M, Hsiung F et al (1998) Dissecting the roles of the Drosophila EGF receptor in eye development and MAP kinase activation. Development 125:3875–3885

    CAS  PubMed  Google Scholar 

  113. Rogers EM, Brennan CA, Mortimer NT et al (2005) Pointed regulates an eye-specific transcriptional enhancer in the Drosophila hedgehog gene, which is required for the movement of the morphogenetic furrow. Development 132:4833–4843. doi:10.1242/dev.02061

    Article  CAS  PubMed  Google Scholar 

  114. Roignant J-Y, Treisman JE (2009) Pattern formation in the Drosophila eye disc. Int J Dev Biol 53:795–804. doi:10.1387/ijdb.072483jr

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Baker NE, Mlodzik M, Rubin GM (1990) Spacing differentiation in the developing Drosophila eye: a fibrinogen-related lateral inhibitor encoded by scabrous. Science 250:1370–1377

    Article  CAS  PubMed  Google Scholar 

  116. Cagan RL, Ready DF (1989) Notch is required for successive cell decisions in the developing Drosophila retina. Genes Dev 3:1099–1112

    Article  CAS  PubMed  Google Scholar 

  117. Baonza A, Casci T, Freeman M (2001) A primary role for the epidermal growth factor receptor in ommatidial spacing in the Drosophila eye. Curr Biol 11:396–404. doi:10.1016/S0960-9822(01)00125-7

    Article  CAS  PubMed  Google Scholar 

  118. Yang L, Baker NE (2001) Role of the EGFR/Ras/Raf pathway in specification of photoreceptor cells in the Drosophila retina. Development 128:1183–1191

    CAS  PubMed  Google Scholar 

  119. Rodrigues AB, Werner E, Moses K (2005) Genetic and biochemical analysis of the role of Egfr in the morphogenetic furrow of the developing Drosophila eye. Development 132:4697–4707. doi:10.1242/dev.02058

    Article  CAS  PubMed  Google Scholar 

  120. Wolff T (2003) EGF receptor signaling: putting a new spin on eye development. Curr Biol 13:R813–R814

    Article  CAS  PubMed  Google Scholar 

  121. Brown KE, Freeman M (2003) Egfr signalling defines a protective function for ommatidial orientation in the Drosophila eye. Development 130:5401–5412. doi:10.1242/dev.00773

    Article  CAS  PubMed  Google Scholar 

  122. Strutt H, Strutt D (2003) EGF signaling and ommatidial rotation in the Drosophila eye. Curr Biol 13:1451–1457

    Article  CAS  PubMed  Google Scholar 

  123. Gaengel K, Mlodzik M (2003) Egfr signaling regulates ommatidial rotation and cell motility in the Drosophila eye via MAPK/Pnt signaling and the Ras effector Canoe/AF6. Development 130:5413–5423. doi:10.1242/dev.00759

    Article  CAS  PubMed  Google Scholar 

  124. Weber U, Pataki C, Mihaly J, Mlodzik M (2008) Combinatorial signaling by the Frizzled/PCP and Egfr pathways during planar cell polarity establishment in the Drosophila eye. Dev Biol 316:110–123. doi:10.1016/j.ydbio.2008.01.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Mirkovic I, Mlodzik M (2006) Cooperative activities of Drosophila DE-cadherin and DN-cadherin regulate the cell motility process of ommatidial rotation. Development 133:3283–3293. doi:10.1242/dev.02468

    Article  CAS  PubMed  Google Scholar 

  126. Brown KE, Baonza A, Freeman M (2006) Epithelial cell adhesion in the developing Drosophila retina is regulated by Atonal and the EGF receptor pathway. Dev Biol 300:710–721. doi:10.1016/j.ydbio.2006.08.003

    Article  CAS  PubMed  Google Scholar 

  127. Robertson F, Pinal N, Fichelson P, Pichaud F (2012) Atonal and EGFR signalling orchestrate rok- and Drak-dependent adherens junction remodelling during ommatidia morphogenesis. Development 139:3432–3441. doi:10.1242/dev.080762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Frankfort BJ, Mardon G (2004) Senseless represses nuclear transduction of Egfr pathway activation. Development 131:563–570. doi:10.1242/dev.00941

    Article  CAS  PubMed  Google Scholar 

  129. Rawlins EL, White NM, Jarman AP (2003) Echinoid limits R8 photoreceptor specification by inhibiting inappropriate EGF receptor signalling within R8 equivalence groups. Development 130:3715–3724

    Article  CAS  PubMed  Google Scholar 

  130. Flores GV, Duan H, Yan H et al (2000) Combinatorial signaling in the specification of unique cell fates. Cell 103:75–85

    Article  CAS  PubMed  Google Scholar 

  131. Tsuda L, Nagaraj R, Zipursky SL, Banerjee U (2002) An EGFR/Ebi/Sno pathway promotes delta expression by inactivating Su(H)/SMRTER repression during inductive notch signaling. Cell 110:625–637

    Article  CAS  PubMed  Google Scholar 

  132. Hayashi T, Xu C, Carthew RW (2008) Cell-type-specific transcription of prospero is controlled by combinatorial signaling in the Drosophila eye. Development 135:2787–2796. doi:10.1242/dev.006189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Nagaraj R, Banerjee U (2007) Combinatorial signaling in the specification of primary pigment cells in the Drosophila eye. Development 134:825–831. doi:10.1242/dev.02788

    Article  CAS  PubMed  Google Scholar 

  134. Kurada P, White K (1998) Ras promotes cell survival in Drosophila by downregulating hid expression. Cell 95:319–329

    Article  CAS  PubMed  Google Scholar 

  135. Bergmann A, Agapite J, McCall K, Steller H (1998) The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling. Cell 95:331–341

    Article  CAS  PubMed  Google Scholar 

  136. Querenet M, Goubard V, Chatelain G et al (2015) Spen is required for pigment cell survival during pupal development in Drosophila. Dev Biol 402:208–215. doi:10.1016/j.ydbio.2015.03.021

    Article  CAS  PubMed  Google Scholar 

  137. Miller DT, Cagan RL (1998) Local induction of patterning and programmed cell death in the developing Drosophila retina. Development 125:2327–2335

    CAS  PubMed  Google Scholar 

  138. Yu S-Y, Yoo SJ, Yang L et al (2002) A pathway of signals regulating effector and initiator caspases in the developing Drosophila eye. Development 129:3269–3278

    CAS  PubMed  Google Scholar 

  139. Wech I, Nagel AC (2005) Mutations in rugose promote cell type-specific apoptosis in the Drosophila eye. Cell Death Differ 12:145–152. doi:10.1038/sj.cdd.4401538

    Article  CAS  PubMed  Google Scholar 

  140. Fan Y, Bergmann A (2014) Multiple mechanisms modulate distinct cellular susceptibilities toward apoptosis in the developing Drosophila eye. Dev Cell 30:48–60. doi:10.1016/j.devcel.2014.05.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Halfar K, Rommel C, Stocker H, Hafen E (2001) Ras controls growth, survival and differentiation in the Drosophila eye by different thresholds of MAP kinase activity. Development 128:1687–1696

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The author thanks Anne-Marie Pret and Kevin Legent for their time and their very helpful critical comments on the manuscript.

Author information

Authors and Affiliations

  1. Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette Cedex, France

    Marianne Malartre

Authors
  1. Marianne Malartre
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marianne Malartre.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Malartre, M. Regulatory mechanisms of EGFR signalling during Drosophila eye development. Cell. Mol. Life Sci. 73, 1825–1843 (2016). https://doi.org/10.1007/s00018-016-2153-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-016-2153-x

Keywords

Search

Navigation