Modeling and computational analysis of EGF receptor-mediated cell communication in Drosophila oogenesis

Stanislav Yefimovic Shvartsman, Cyrill B. Muratov, Douglas A. Lauffenburger

Research output: Contribution to journalReview article

95 Scopus citations

Abstract

Autocrine signaling through the Epidermal Growth Factor Receptor (EGFR) operates at various stages of development across species. A recent hypothesis suggested that a distributed network of EGFR autocrine loops was capable of spatially modulating a simple single-peaked input into a more complex two-peaked signaling pattern, specifying the formation of a pair organ in Drosophila oogenesis (two respiratory appendages on the eggshell). To test this hypothesis, we have integrated genetic and biochemical information about the EGFR network into a mechanistic model of transport and signaling. The model allows us to estimate the relative spatial ranges and time scales of the relevant feedback loops, to interpret the phenotypic transitions in eggshell morphology and to predict the effects of new genetic manipulations. We have found that the proposed mechanism with a single diffusing inhibitor is sufficient to convert a single-peaked extracellular input into a two-peaked pattern of intracellular signaling. Based on extensive computational analysis, we predict that the same mechanism is capable of generating more complex patterns. At least indirectly, this can be used to account for more complex eggshell morphologies observed in related fly species. We propose that versatility in signaling mediated by autocrine loops can be systematically explored using experiment-based mechanistic models and their analysis.

Original languageEnglish (US)
Pages (from-to)2577-2589
Number of pages13
JournalDevelopment
Volume129
Issue number11
StatePublished - Aug 23 2002

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Keywords

  • Autocrine loops
  • Drosophila
  • EGFR
  • Mathematical modeling

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