Cell Fate--The Specification/Differentiation Interface

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DESCRIPTION (provided by applicant): Understanding precisely how cell fate determination mechanisms control the differentiative programs of individual cell types is the long-term goal of this project. The mechanosensory bristle organs that constitute the largest fraction of the Drosophila adult peripheral nervous system offer, we believe, a particularly accessible and advantageous setting in which to investigate the interface between cell fate specification and cell differentiation. The stereotyped cell lineage that gives rise to each organ generates, in an extremely limited space and time, multiple distinct cell types, at least three of which depend for their determination on the action of the same cell fate specification system, the Notch signaling pathway. Thus, the development of these bristle organs offers an unusually favorable opportunity to unravel specifically how cell-type diversity is created and realized. Our preliminary studies have indicated unmistakably that transcriptional regulation is the principal mechanism underlying the determination and execution of distinct programs of cell differentiation in the bristle lineage, and the proposed research program has been designed accordingly. The project has three major objectives, all focusing on the socket and shaft cells, sister cells that arise in a Notch-dependent asymmetric cell division: (1) Analyze transcriptional cis-regulatory modules that direct specific gene expression in the socket and shaft cells. (2) Identify novel targets of direct transcriptional regulation by Suppressor of Hairless and D-Pax2 in the socket and shaft cells. (3) Define systematically the gene expression programs of developing socket and shaft cells. By focusing on a particularly favorable cell fate specification/differentiation system, this research project offers the prospect of significant advances in our mechanistic understanding of how cell type diversity is generated.