POZ-ZF Transcription Factors in Signal Transduction and Development.

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The development of multicellular organisms involves a highly coordinated and controlled series of events that regulates the proliferation and differentiation of cells into tissues and organs with specific functions. These events require communication between cells via a phenomenon called signal transduction, which often culminates in the nucleus with changes in gene expression controlled by proteins called transcription factors. These changes in gene expression in turn trigger cells to respond and either divide, differentiate or become motile. Although several signaling pathways have been identified that regulate the crucial stages of early vertebrate development, it is unclear how these various signals are integrated to elicit the specific cellular responses needed for this process. Recently several members of the family of POZ-zinc finger (POZ-ZF) transcription factors have been linked to signaling pathways that are essential for vertebrate development. Additionally, data from my laboratory revealed that frog embryos lacking different POZ-ZF proteins displayed striking early and late developmental defects. These observations led to our hypothesis that POZ-ZF proteins are important effectors of signaling transduction during early vertebrate development. Since little is known about how POZ-ZF proteins are mechanistically connected to established signaling pathways, our Discovery research program focuses on deciphering "The Role and Basic Mechanisms of Action of POZ-ZF Transcription Factors in Vertebrate Development" using the frog Xenopus laevis as a model organism. Xenopus is a proven model system for such studies because frogs are inexpensive, the embryos are very easy to manipulate for protein knockdown and overexpression studies, and the Xenopus versions of the mammalian POZ-ZF proteins we are studying are very similar. To achieve our research goals, we will utilize a variety of cutting-edge and established molecular cell biology skills that are essential for success in the Canadian and International biology research arena.