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, become motile or die. Although several signaling pathways have been identified that regulate the crucial stages of early vertebrate development, it remains unclear how these various signals are integrated to elicit the specific cellular responses needed during development, and to ensure a health viable organism/vertebrate. One unique family of transcription factors (POZ-zinc finger, POZ-ZF) have been linked to signaling pathways that are essential for vertebrate development. These transcription factors interact with each other and regulate numerous target genes. 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 downstream 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 cell lines and 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 and genetic techniques, and functional assays. Experimentally linking POZ-ZF proteins to established developmental signaling pathways and morphogenetic events would provide novel insight on the crosstalk between signaling pathways in early vertebrate development. Our findings would also add to the knowledge base of POZ-ZF protein function in vertebrates, and significantly advance our knowledge and understanding of fundamental developmental processes that are shared by all vertebrates. My Discovery research program is designed to train, mentor and produce at least seven highly qualified personnel (3 MSc/PhD, 3 BSc) with competitive research, critical thinking and communication skills; skills that are essential for successful careers in the Canadian and International Research & Development arena.