Regulation of tissue morphogenesis by non-canonical steroid hormone signaling in Drosophila

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During the development of embryos, there is a need to close holes in sheets of cells called epithelia. Failure of such closure events can lead to birth defects such as spina bifida and cleft lip and palate. Developmental epithelial closure is very similar to the healing of a wound, and the two processes use the same cellular machinery. Indeed, developmental epithelial closures can be considered as wound healing events. We are studying genes involved in a developmental wound healing event called dorsal closure that occurs during embryonic development in the fruit fly Drosophila. We use this organism due to the advanced genetic tools available and the ease with which dorsal closure can be observed. This work is relevant to human wound healing, as much of the cellular machinery has already been characterized, and is the same in humans and fruit flies. We are asking an important question with regard to Drosophila dorsal closure: how does communication between cells lead to smooth closure of the wound? In particular, we are working to understand how a steroid hormone called ecdysone can regulate the timing of genes that are being turned on to close the hole. Preliminary results indicate that ecdysone acts through an atypical pathway to turn on these genes, but interestingly, the same pathway is sometimes used by human steroid hormones such as estrogen. This result suggests that steroid hormones have been using this atypical pathway for hundreds of millions of years, before fruit flies diverged from humans. There are a number of potential benefits from this research. First, we can learn about the evolution of steroid hormone signaling, a cell communication process important in development and disease. Second, it will increase our understanding of the cellular events behind the closure of epithelial sheets both during development and in the healing of wounds. Third, this work will give important insight into the regulation of the movement and shape of epithelial cells, which is a key process in building a multicellular organism.