Bidirectional communication between tissues regulating morphogenesis in a Drosophila model of wound healing

Drosophila embryonic dorsal closure is a developmental epithelial fusion event that resembles vertebrate processes such as neural tube closure and wound healing. Dorsal closure involves the migration of two epidermal sheets to close an epidermal hole occupied by a tissue called the amnioserosa. The successful completion of this process requires a signalling network that involves communication between the amnioserosa and the dorsal epidermis, and the Dpp and JNK pathways are two central participants. Dorsal closure is driven in part by myosin-dependent cell shape change in both the dorsal epidermis and the amnioserosa. Consistent with this, myosin heavy chain expression from the zipper (zip) gene is upregulated in these two tissues in a Dpp-dependent manner and we believe that zip regulation is a critical component of dorsal closure. We have taken a candidate gene approach to identify new participants in zip regulation during dorsal closure. We have established that Egfr acts as a brake on dorsal closure in that it inhibits the expression of both dpp and zip. Egfr is itself negatively regulated by the non-receptor tyrosine kinase Ack, which may be reducing Egfr levels by promoting its endocytosis. Previous work suggests that a diffusible signal from the amnioserosa regulates gene expression in both the amnioserosa and the dorsal epidermis. We have established that this diffusible signal is the steroid hormone ecdysone, which cooperates with JNK signalling to turn on zip expression. We have also determined that Dpp secreted from the dorsal epidermis turns on ecdysone production in the amnioserosa by promoting expression of the ecdysone biosynthetic enzyme Spook. Thus, we have uncovered reciprocal signalling between two tissues leading to coordinated morphogenesis. We have further established that ecdysone is acting in a non-canonical manner in its cooperation with JNK signalling in this process. We provide genetic and immunohistochemical evidence that the ecdysone receptor turns on zip by complexing with the JNK-activated transcription factor AP-1. Using the proximity ligation assay, we visualize this complex in the nuclei of amnioserosa and dorsal epidermal cells during dorsal closure. Our findings may provide clues to the signalling events occurring during other epithelial fusions.What we found in this project could help to better understand the bidirectional communication that occurs between the amnioserosa and dorsal epidermis at the level of signaling network allowing coordinated morphogenesis of the two tissues through the regulation of actomyosin contractility.