POZ-ZF transcription factors in cell adhesion 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. Events such as cell-cell adhesion and signal transduction within cells culminate 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 gastrulation, a key event in early development, it is unclear how the various signals are integrated to elicit the specific cellular responses needed for this process. Recently at least two POZ-zinc finger (POZ-ZF) transcription factors have been linked to Wnt signaling pathways that are absolutely required for vertebrate development. This led to our hypothesis that POZ-ZF proteins play a role in integrating important signaling cascades during early vertebrate embryogenesis. Our research program seeks to understand "The Role and Basic Mechanisms of Action of the POZ-ZF family of Transcription Factors in Cell Adhesion and Vertebrate Development". Our Discovery Grant focuses on elucidating the developmental role of vertebrate POZ-ZF proteins using the frog Xenopus laevis as a model organism. Xenopus is a good model system because frogs are inexpensive, easy to manipulate for protein knockdown and overexpression studies and there are Xenopus homologs to many of the mammalian POZ-ZF proteins implicated in development. Preliminary data from my laboratory revealed that frog embryos lacking different POZ-ZF proteins displayed striking early developmental defects, supporting the hypothesis that they play an important role in early vertebrate development. The proposed studies will provide novel insight on early vertebrate development and gastrulation, and add to the knowledge base of POZ-ZF protein function in vertebrates as a whole.