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Development 129, 2577-2589 (2002)
© 2002 The Company of Biologists Limited

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

Stanislav Y. Shvartsman1,*, Cyrill B. Muratov2 and Douglas A. Lauffenburger3

1 Department of Chemical Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA
2 Department of Mathematical Sciences and Center for Applied Mathematics and Statistics, New Jersey Institute of Technology, Newark, NJ 07102, USA
3 Biological Engineering Division and Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

*Author for correspondence (e-mail: stas{at}princeton.edu)

Accepted 11 March 2002

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.

Key words: Drosophila, EGFR, Mathematical modeling, Autocrine loops




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© The Company of Biologists Ltd 2002