CONTROL OF CELL DIFFERENTIATION BY NOTCH SIGNALING

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The Notch signaling pathway plays an key role in mediating cell-cell interactions in many animals, including mammals, Xenopus, C. elegans, and Drosophila. In many developing tissues, these Notch-mediated cell signaling processes are essential for proper assignment of cell fates. Dysfunctional Notch activity in humans is associated with cancers, including acute lymphoblastic leukemia, acute myeloblastic leukemia and ovarian carcinoma. One well-studied instance of Notch signaling is in regulating cell fate specification among the four cells of the mechanosensory bristle in Drosophila. The broadly expressed transcription factor Suppressor of Hairless [Su(H)] is the primary transducer of the Notch signal in these cells. We have found that Su(H) mRNA and protein levels are greatly increased in only one cell type in Drosophila, the socket cell of the mechanosensory bristle, and that this up-regulation seems to be due to a highly cell-specific enhancer which is active only in the socket cell. We wish to study the differentiation of the socket cell as a model system for investigating the way in which highly conserved, multipurpose signaling pathways can direct species-specific, tissue-specific, and cell-specific differentiative programs. We hope to use the Su(H) socket enhancer in several ways, using both genetic and biochemical approaches, to allow us to identify the links between cell signaling and cell differentiation.