POU transcription factors have been shown to be important in the regulation of cell fate decisions during development. We have focused on understanding the function of one POU domain gene, XIPOU 2 , in early neural development. XIPOU 2 is immediately downstream in the neural inductive signaling pathway for noggin. Our current goal is to identify noggin inducible elements in the XIPOU 2 promoter. XIPOU 2's temporal and spatial pattern of expression suggests that it may be regulatory in the neural inductive process. Misexpressing XIPOU 2 in ventral ectoderm results in a cell fate change from an epidermal to neuronal phenotype, demonstrating XIPOU 2's potential role as a master regulator in neurogenesis. We have examined the role of XIPOU 2 in Spemann's organizer by overexpressing the XIPOU 2 gene product in embryos. The overexpression of XIPOU 2 leads to a suppression of dorsal gene function in gastrulating Xenopus embryos, which results in a """"""""headless"""""""" phenotype. We have also characterized a novel POU gene in zebrafish, taichi. The expression pattern of taichi during development and in the adult brain is consistent with its potential role in regulating the establishment and/or maintenance of neural stem cells. Taichi expression is associated with proliferating, non-differentiated cells of the brain. This cell population can be labeled by BrdU, and does not express two markers of neural differentiation, acetylated tubulin and neurofilament protein. We are characterizing these cells further using another marker that is co-expressed with taichi, NRP-1 (an RNA binding protein). To further understand the role of stem cells in mammalian development, we are attempting to clone a mouse homolog of taichi.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
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State
Country
United States
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