PATTERNING BY EGF RECEPTOR: MODELS FROM DROSOPHILA DEVELOPMENT - Complex Systems Science in Biomedicine - page 320

2.3

PATTERNING BY EGF RECEPTOR: MODELS
FROM DROSOPHILA DEVELOPMENT

Lea A. Goentoro and Stanislav Y. Shvartsman
Lewis-Sigler Institute for Integrative Genomics,
Princeton University, Princeton, New Jersey

The epidermal growth factor receptor (EGFR) belongs to a large class of receptor tyro-
sine kinases. Abnormal EGFR signaling is associated with severe developmental defects
and many types of cancers. Many individual molecules mediating the EGFR-induced re-
sponses 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 descrip-
tion of the EGFR network in tissues. Systems-level descriptions are impossible without
quantitative models. Even the simplest models of EGFR signaling in tissues must simul-
taneously account for ligand transport, binding, signal transduction, and gene expression.
Given this complexity, such tissue-level models are difficult to test; therefore, they re-
quire appropriate experimental paradigms for their validation. We suggest that model or-
ganisms of developmental genetics, such as the fruit fly Drosophila melanogaster , can be
used as experimental systems for the development and validation of computational de-
scriptions of EGFR signaling in tissues.

1.

INTRODUCTION

The epidermal growth factor receptor (EGFR) is an evolutionarily con-
served regulator of epithelial tissues. The first identified receptor tyrosine kinase

Stanislav Y. Shvartsman, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Carl
Icahn Laboratory, Washington Road, Princeton, NJ 08544; [phone]; [e-mail].

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