Generation of tissue from progenitor cells (stem cells) is a complex process, often requiring elaborate communication events between cells located near each other or at some distance away. Studies of skin development, and in particular the development of the hair follicle, have served as a model for such interactions and yet no precise information exists regarding the molecular details underlying the mechanisms by which acquisition of diverse cell fates within the hair follicle occurs. In this proposal we offer to investigate the potential of individual progenitor cells to contribute to any of the six differentiated cell types within the follicle. In addition, we will investigate the role of the Notch pathway in follicular cell fate selection. The Notch receptor is involved in a short-range cell-cell communication pathway which is able to amplify small, sometimes stochastic differences between equivalent cells, into an all or nothing developmental outcome. This pathway have been shown to hold the ky for fate allocation during Drosophila and vertebrate neurogenesis, in vertebrate hematopoiesis and in large number of other systems. We will establish whether Notch, expressed in hair follicles, plays a similar role in determining the identity of hair follicle cells. Combined, we hope these studies will further our knowledge of how individual progenitor cells at the base of a follicle contributes differentiated progenies to the hair shaft and provide the basis for future studies, aimed at understanding how cells integrate signals from multiple singling pathways to differentiate properly.
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