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Patterning by EGF Receptor: Models from Drosophila Development

  • Lea A. Goentoro
  • Stanislav Y. ShvartsmanEmail author
Part of the Topics in Biomedical Engineering International Book Series book series (ITBE)

Abstract

The epidermal growth factor receptor (EGFR) belongs to a large class of receptor tyrosine kinases. Abnormal EGFR signaling is associated with severe developmental defects and many types of cancers. Many individual molecules mediating the EGFR-induced responses became drug targets in oncology and other areas of medicine. However, neither the contribution of EGFR to tissue morphogenesis in development nor the exact role of deregulated EGFR signaling in diseases is understood at this time. The key challenge is to integrate the existing molecular and cellular information into a systems-level description of the EGFR network in tissues. Systems-level descriptions are impossible without quantitative models. Even the simplest models of EGFR signaling in tissues must simultaneously account for ligand transport, binding, signal transduction, and gene expression. Given this complexity, such tissue-level models are difficult to test; therefore, they require appropriate experimental paradigms for their validation. We suggest that model organisms of developmental genetics, such as the fruit fly Drosophila melanogaster, can be used as experimental systems for the development and validation of computational descriptions of EGFR signaling in tissues.

Keywords

Epidermal Growth Factor Receptor Follicle Cell Epidermal Growth Factor Receptor Activity Epidermal Growth Factor Receptor Pathway Oocyte Nucleus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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7. References

  1. 1.
    Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. 2003. Epidermal growth factor receptor: mechanisms of activation and signaling. Exp Cell Res 284(4):31–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Yarden Y, Sliwkowski MX. 2001. Untangling the ErbB signalling network. Nature Rev Mol Cell Biol 2:127–137.CrossRefGoogle Scholar
  3. 3.
    Pierce KL, Tohgo A, Ahn S, Field ME, Luttrell LM, Lefkowitz RJ. 2001. Epidermal growth factor (EGF) receptor-dependent ERK activation by G protein-coupled receptors: a co-culture system for identifying intermediates upstream and downstream of heparin-binding EGF shedding. J Biol Chem 276(25):23155–23160.PubMedCrossRefGoogle Scholar
  4. 4.
    Vermeer PD, Einwalter LA, Moninger TO, Rokhlina T, Kern JA, Zabner J, Welsh MJ. 2003. Segregation of receptor and ligand regulates activation of epithelial growth factor receptor. Nature 422(6929):322–326.PubMedCrossRefGoogle Scholar
  5. 5.
    Wiley HS, Shvartsman SY, Lauffenburger DA. 2003. Computational modeling of the EGF receptor system: a paradigm for systems biology. Trends Cell Biol 13(1):43–50.PubMedCrossRefGoogle Scholar
  6. 6.
    Lander AD, Nie W, Wan FY. 2002. Do morphogen gradients arise by diffusion? Dev Cell 2(6):785–796.PubMedCrossRefGoogle Scholar
  7. 7.
    Shilo BZ. 2003. Signaling by the Drosophila epidermal growth factor receptor pathway during development. Exp Cell Res 284(1):140–149.PubMedCrossRefGoogle Scholar
  8. 8.
    Casci T, Freeman M. 1999. Control of EGF receptor signalling: lessons from fruitflies. Cancer Metastasis Rev 18(2):181–201.PubMedCrossRefGoogle Scholar
  9. 9.
    Klein DE, Nappi VM, Reeves GT, Shvartsman SY, Lemmon MA. 2004. Argos inhibits epidermal growth factor receptor signaling by ligand sequestration. Nature 430(730):1040–1044.PubMedCrossRefGoogle Scholar
  10. 10.
    Golembo M, Yarnitzky T, Volk T, Shilo BZ. 1999. Vein expression is induced by the EGF receptor pathway to provide a positive feedback loop in patterning the Drosophila embryonic ventral ectoderm. Genes Dev 13(2):158–162.PubMedGoogle Scholar
  11. 11.
    Wasserman JD, Freeman M. 1998. An autoregulatory cascade of EGF receptor signaling patterns the Drosophila egg. Cell 95(3):355–364.PubMedCrossRefGoogle Scholar
  12. 12.
    Schweitzer R, Shilo BZ. 1997. A thousand and one roles for the Drosophila EGF receptor. Trends Genet 13(5):191–196.PubMedCrossRefGoogle Scholar
  13. 13.
    Golembo M, Raz E, Shilo BZ. 1997. The Drosophila embryonic midline is the site of Spitz processing, and induces activation of the EGF receptor in the ventral ectoderm. Development 122(11):3363–3370.Google Scholar
  14. 14.
    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(1):223–230.PubMedGoogle Scholar
  15. 15.
    Nambu JR, Franks RG, Hu S, Crews ST. 1990. The single-minded gene of Drosophila is required for the expression of genes important for the development of CNS midline cells. Cell 63(1):63–57.PubMedCrossRefGoogle Scholar
  16. 16.
    Lee JR, Urban S, Garvey CF, Freeman M. 2001. Regulated intracellular ligand transport and proteolysis control EGF signal activation in Drosophila. Cell 107(2):161–171.PubMedCrossRefGoogle Scholar
  17. 17.
    Dobens LL, Raftery LA. 2000. Integration of epithelial patterning and morphogenesis in Drosophila oogenesis. Dev Dyn 218(1):80–93.PubMedCrossRefGoogle Scholar
  18. 18.
    Spradling, AC. 1993. Developmental genetics of oogenesis. In The development of drosophila melanogaster, pp. 1–70. Ed. M Bate, AM Arias. Cold Spring Harbor Laboratory Press, Plainview, New York.Google Scholar
  19. 19.
    Queenan AM, Ghabrial A, Schupbach T. 1997. Ectopic activation of torpedo/Egfr, a Drosophila receptor tyrosine kinase, dorsalizes both the eggshell and the embryo. Development 124(19):3871–3880.PubMedGoogle Scholar
  20. 20.
    Nilson LA, Schupbach T. 1999. EGF receptor signaling in Drosophila oogenesis. Curr Top Dev Biol 44:203–243.PubMedCrossRefGoogle Scholar
  21. 21.
    Neuman-Silberberg FS, Schupbach T. 1993. The Drosophila dorsoventral patterning gene gurken produces a dorsally localized RNA and encodes a TGF alpha-like protein. Cell 75(1):165–174.PubMedCrossRefGoogle Scholar
  22. 22.
    Montell DJ, Keshishian H, Spradling AC. 1993. Laser ablation studies of the role of the Drosophila oocyte nucleus in pattern formation. Science 254(5029):290–293.CrossRefGoogle Scholar
  23. 23.
    Guichet A, Peri F, Roth S. 2001. Stable anterior anchoring of the oocyte nucleus is required to establish dorsoventral polarity of the Drosophila egg. Dev Biol 237(1):93–106.PubMedCrossRefGoogle Scholar
  24. 24.
    Peri F, Roth S. 2000. Combined activities of Gurken and Decapentaplegic specify dorsal chorion structures of the Drosophila egg. Development 127(4):841–850.PubMedGoogle Scholar
  25. 25.
    Pribyl M, Muratov CB, Shvartsman SY. 2003. Discrete models of autocrine signaling in epithelial layers. Biophys J 83(6):3659–65.Google Scholar
  26. 26.
    Pribyl M, Muratov CB, Shvartsman SY. 2003. Transitions in the model of epithelial patterning. Dev Dyn 226(1):155–159.PubMedCrossRefGoogle Scholar
  27. 27.
    Pribyl M, Muratov CB, Shvartsman SY. 2003. Long-range signal transmission in autocrine relays. Biophys J 84(2):883–896.PubMedGoogle Scholar
  28. 28.
    Shvartsman SY, Wiley HS, Deen WM, Lauffenburger DA. 2001. Spatial range of autocrine signaling: modeling and computational analysis. Biophys J 81(4):1854–1867.PubMedCrossRefGoogle Scholar
  29. 29.
    Shvartsman SY, Hagan MP, Yacoub A, Dent P, Wiley HS, Lauffenburger DA. 2002. Autocrine loops with positive feedback enable context-dependent cell signaling. Am J Physiol Cell Physiol 282(3):C545–C559.PubMedGoogle Scholar
  30. 30.
    Shvartsman SY, Muratov CB, Lauffenburger DA. 2002. Modeling and computational analysis of EGF receptor-mediated cell communication in Drosophila oogenesis. Development 129(11):2577–2589.PubMedGoogle Scholar
  31. 31.
    Bergmann A, Tugentman M, Shilo H. 2002. Regulation of cell number by MAPK-dependent control of apoptosis: a mechanism for trophic survival signaling. Dev Cell 2(2):159–170.PubMedCrossRefGoogle Scholar
  32. 32.
    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(12):1518–1529.PubMedCrossRefGoogle Scholar
  33. 33.
    Freeman M. 1997. Cell determination strategies in the Drosophila eye. Development 124(2):261–270.PubMedGoogle Scholar
  34. 34.
    Pai LM, Barcelo G, Schupbach T. 2000. D-cbl, a negative regulator of the Egfr pathway, is required for dorsoventral patterning in Drosophila oogenesis. Cell 103(1):51–61.PubMedCrossRefGoogle Scholar
  35. 35.
    Peri F, Technau M, Roth S. 2002. Mechanisms of Gurken-dependent pipe regulation and the robustness of dorsoventral patterning in Drosophila. Development 129(12):2965–2975.PubMedGoogle Scholar
  36. 36.
    James KE, Dorman JB, Berg CA. 2002. Mosaic analyses reveal the function of Drosophila Ras in embryonic dorsoventral patterning and dorsal follicle cell morphogenesis. Development 129(9):209–222.Google Scholar
  37. 37.
    Dowd CJ, Cooney CL, Nugent MA. 1999. Heparan sulfate mediates bFGF transport through basement membrane by diffusion with rapid reversible binding. J Bio Chem 274(8):5236–5244.CrossRefGoogle Scholar
  38. 38.
    Berg HC. 1983. Random walks in biology. Princeton University Press, Princeton.Google Scholar
  39. 39.
    Wiley HS. 2003. Trafficking of the ErbB receptors and its influence on signaling. Exp Cell Res 284(1):78–88.PubMedCrossRefGoogle Scholar
  40. 40.
    Wiley HS, Burke PM. 2001. Regulation of receptor tyrosine kinase signaling by endocytic trafficking. Traffic 2(1):12–18.PubMedCrossRefGoogle Scholar
  41. 41.
    Abramowitz M, Stegun IA. 1964. Handbook of mathematical tables with formulas, graphs, and mathematical tables. Government Printing Office, Washington, DC.Google Scholar
  42. 42.
    Seto ES, Bellen HJ, Lloyd TE. 2002. When cell biology meets development: endocytic regulation of signaling pathways. Genes Dev. 16(11):1314–1336.PubMedCrossRefGoogle Scholar
  43. 43.
    Lloyd TE, Atkinson R, Wu MN, Zhou Y, Pennetta G, Bellen HJ. 2002. Hrs regulates endosome membrane invagination and tyrosine kinase receptor signaling in Drosophila. Cell 108(2):261–269.PubMedCrossRefGoogle Scholar
  44. 44.
    Entchev EV, Gonzalez-Gaitan MA. 2002. Morphogen gradient formation and vesicular trafficking. Traffic 3(2):98–109.PubMedCrossRefGoogle Scholar
  45. 45.
    Peri F, Bokel C, Roth S. 1999. Local gurken signaling and dynamic MAPK activation during Drosophila oogenesis. Mech Dev 81(1–2):75–88.PubMedCrossRefGoogle Scholar
  46. 46.
    Sapir A, Schweitzer R, Shilo BZ. 1998. Sequential activation of the EGF receptor pathway during Drosophila oogenesis establishes the dorsoventral axis. Development 125(2):191–200.PubMedGoogle Scholar
  47. 47.
    Hsu T, McRackan D, Vincent TS, Gert de Couet H. 2001. Drosophila Pin1 prolyl isomerase Dodo is a MAP kinase signal responder during oogenesis. Nature Cell Biol 3(6):538–543.PubMedCrossRefGoogle Scholar
  48. 48.
    Mantrova EY, Hsu T. 1998. Down-regulation of transcription factor CF2 by Drosophila Ras/MAP kinase signaling in oogenesis: cytoplasmic retention and degradation. Genes Dev 12(8):1166–1175.PubMedGoogle Scholar
  49. 49.
    Sturtevant MA, Roark M, O’Neill JW, Biehs B, Colley N, Bier E. 1996. The Drosophila rhomboid protein is concentrated in patches at the apical cell surface. Dev Biol 174(2):298–309.PubMedCrossRefGoogle Scholar
  50. 50.
    Reich A, Sapir A, Shilo BZ. 1999. Sprouty, a general inhibitor of receptor tyrosine kinase signaling. Development 126(18):413–447.Google Scholar
  51. 51.
    Deng WM, Bownes M. 1997. Two signalling pathways specify localised expression of the Broad-Complex in Drosophila eggshell patterning and morphogenesis. Development 124(22):4639–4647.PubMedGoogle Scholar
  52. 52.
    Perrimon N, Duffy, JD. 1998. Developmental biology: sending all the right signals. Nature 396(6706):18–19.PubMedCrossRefGoogle Scholar
  53. 53.
    Hinton HE. 1981, Biology of insect eggs, Vol. 1. Pergamon Press, New York.Google Scholar
  54. 54.
    Dent P, Reardon D, Park J, Bowers G, Logsdon C, Valerie K, Schmidt-Ullrich R. 1999. Radiation-induced release of transforming growth factor-α activates the epidermal growth factor receptor and mitogen-activated protein kinase pathway in carcinoma cells, leading to increased proliferation and protection from radiation-induced cell death. Mol Biol Cell 10:2493–2506.PubMedGoogle Scholar
  55. 55.
    Lee H, R Akita W, Sliwkowski MX, Maihle NJ. 2001. A naturally occurring secreted human ErbB3 receptor isoform inhibits heregulin-stimulated activation of ErbB2, ErbB3, and ErbB4. Cancer Res 61(11):4467–4473.PubMedGoogle Scholar
  56. 56.
    Baron AT, Cora EM, Lafky JM, Boardman CH, Buenafe MC, Rademaker A, Liu D, Fishman DA, Podratz KC, Maihle NJ. 2003. Soluble epidermal growth factor receptor (sEGFR/sErbB1) as a potential risk, screening, and diagnostic serum biomarker of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 12(2):103–13.PubMedGoogle Scholar

Copyright information

© Springer Inc. 2006

Authors and Affiliations

  1. 1.Lewis-Sigler Institute for Integrative GenomicsPrinceton UniversityPrinceton

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