Genetics of Corticotroph Development in Zebrafish

Cedars-Sinai Medical Center, West Hollywood CA

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Abstract

DESCRIPTION (provided by applicant): Corticotroph ontogeny during vertebrate development involves molecular pathways distinct from other pituitary cell lineages. The critical determinants of corticotroph differentiation remain largely unclear. Both transcription factors and soluble molecules signaling via Jak/STAT pathways are involved in corticotroph development and pro-opiomelanocortin (POMC) expression. Using POMC expression as an entry point, I propose to study genetic and molecular mechanisms underlying corticotroph determination and differentiation in zebrafish. The aims of this K08 proposal are (1) to elucidate the critical roles of STAT 3 in POMC lineage development; (2) to perform a genetic screen to identify and characterize essential genes required for development of POMC lineage. The latter aim will be achieved through participation in a NIH-funded organ-specific genetic screen that utilizes live transgenic zebrafish harboring fluorescent tissues. Transgenic zebrafish expressing green fluorescent protein driven by the POMC promoter offer a unique in vivo model allowing a detailed genetic analysis of POMC-specific cells in living embryos. As the candidate for this proposal, I am currently a fellow in the Division of Endocrinology, Cedars- Sinai Medical Center (CSMC), UCLA and will complete my fellowship in June 2003. Through the proposed studies, I will expand my knowledge of general and neuro- endocrinology, especially pituitary developmental biology, and further a broad training in molecular biology, genetics, embryology and endocrinology. By the end of this award, I will be eminently trained to undertake independent basic research in pituitary development and to pursue a productive research career in academic medicine. The faculty at CSMC and UCLA have excellent reputations in both strong basic research and training physicians to develop independent careers in academic medicine. I will be mentored by both endocrine and developmental biology faculty at CSMC and UCLA, which will provide synergistic enrichment for this K08 application. CSMC has well-established programs related to my proposal and research interests and is fully committed to sustain my research career development in an environment of academic excellence.