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First published online 29 July 2009
doi: 10.1242/dev.039545

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Feedback control of the EGFR signaling gradient: superposition of domain-splitting events in Drosophila oogenesis

Lewis Sigler Institute and Department of Chemical Engineering, Carl Icahn Laboratory, Washington Road, Princeton University, Princeton, NJ 08544, USA.

^* Author for correspondence (stas{at}princeton.edu)

Accepted 25 June 2009

The morphogenesis of structures with repeated functional units, such as body segments and appendages, depends on multi-domain patterns of cell signaling and gene expression. We demonstrate that during Drosophila oogenesis, the two-domain expression pattern of Broad, a transcription factor essential for the formation of the two respiratory eggshell appendages, is established by a single gradient of EGFR activation that induces both Broad and Pointed, which mediates repression of Broad. Two negative-feedback loops provided by the intracellular inhibitors of EGFR signaling, Kekkon-1 and Sprouty, control the number and position of Broad-expressing cells and in this way influence eggshell morphology. Later in oogenesis, the gradient of EGFR activation is split into two smaller domains in a process that depends on Argos, a secreted antagonist of EGFR signaling. In contrast to the previously proposed model of eggshell patterning, we show that the two-domain pattern of EGFR signaling is not essential for specifying the number of appendages. Thus, the processes that define the two-domain patterns of Broad and EGFR activation are distinct; their actions are separated in time and have different effects on eggshell morphology.

Key words: Feedback, Feedforward, EGFR, Argos, Sprouty, Kekkon-1, Rhomboid, Pattern formation, Oogenesis

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