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 prosurvival signaling molecules released from locations determined by patterning information. In wild-type embryos, the segmentation cascade elicits the segmental production of several epidermal growth factor receptor (EGFR) ligands, including the transforming growth factor Spitz (TGFα), and the neuregulin, Vein. This leads to an undulating pattern of signaling activity, which prevents expression of the proapoptotic gene head involution defective (hid) throughout the epidermis. In segmentation mutants, where specific peaks of EGFR ligands fail to form, gaps in signaling activity appear, leading to coincident hid up-regulation 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.
Highlights
Defective cells are often eliminated by apoptosis during development and tissue homeostasis [1,2,3,4]
In wild-type embryos, the segmentation cascade elicits the segmental production of several epidermal growth factor receptor (EGFR) ligands, including the transforming growth factor Spitz (TGFα), and the neuregulin, Vein
Correct patterning information leads to the segmentally repeated production of survival signals, which activate the epidermal growth factor receptor, and this system is disrupted in patterning mutants leading to reproducible patterns of apoptosis
Summary
Defective cells are often eliminated by apoptosis during development and tissue homeostasis [1,2,3,4]. Excess apoptosis is seen in mutants that lack essential developmental determinants, a phenomenon that has been observed in a variety of model organisms, including zebrafish embryos lacking the signaling molecule Sonic Hedgehog [6], mice lacking the negative Wnt signaling regulator Adenomatous polyposis coli (APC) in the developing neural crest [7], and Drosophila segmentation mutants [8,9,10,11,12]. These observations have suggested the existence of a quality control system that detects conflicting or nonsense patterning inputs and, as a result, initiates apoptosis in response. We take advantage of the genetic tools in Drosophila to investigate how apoptosis is triggered in mispatterned epidermal cells
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