EGFR signaling coordinates patterning with cell survival during Drosophila epidermal development

Abstract

Extensive apoptosis is often seen in patterning mutants, suggesting that tissues can detect and eliminate potentially harmful mis-specified cells. Here we show that the pattern of apoptosis in the embryonic epidermis of Drosophila is not a response to fate mis-specification but can instead be explained by the limiting availability of pro-survival signalling molecules released from locations determined by patterning information. In wild type embryos, the segmentation cascade elicits the segmental production of several EGFR ligands, including the TGF-alpha, Spitz and the Neuregulin, Vein. This leads to an undulating pattern of signalling activity, which prevents expression of the pro-apoptotic gene hid throughout the epidermis. In segmentation mutants, where specific peaks of EGFR ligands fail to form, gaps in signalling activity appear, leading to coincident hid upregulation and subsequent cell death. These data provide a mechanistic understanding of how cell survival, and thus appropriate tissue size, is made contingent on correct patterning.