Regeneration of the Drosophila epidermal barrier after wounding

Abstract

An epidermal wound provides signals that initiate a variety of localized responses that in favorable circumstances results in regeneration and repair of the wound. The Drosophila melanogaster embryonic epidermis provides an excellent system to discover new genes that regulate wound‐healing processes. Using fluorescent epidermal “wound” reporters that are locally activated around wound sites, we have screened almost 5,000 Drosophila mutants for functions required to activate or delimit wound‐induced transcriptional responses to a local zone of epidermal cells. Among the seven new genes required to delimit the spread of wound responses are Flotillin‐2 and Src‐42A. These two genes are also sufficient, when overexpressed at high levels, to inhibit wound‐induced transcription in epidermal cells. One new gene required to activate epidermal wound reporters encodes Dual oxidase, an enzyme that produces hydrogen peroxide. We also find that four biochemical treatments (a serine protease, a Src kinase inhibitor, methyl B‐cyclodextrin, and hydrogen peroxide) are sufficient to globally activate epidermal wound regeneration genes in Drosophila embryos. Our results define new genetic functions, and the interactions among them, that regulate the local transcriptional response to puncture wounds.