Pituitary tumorgenesis is likely to be associated with mutations or derangements of normal corticotrophspecific regulatory pathways. Understanding how corticotroph-lineage develops in normal embryos will help elucidate mechanisms underlining corticotroph tumor ontogeny. 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 proposal are (1) to elucidate the critical roles of STAT 3 in POMC lineage development; (2) to participate in a genetic screen to identify and characterize essential genes required for development of POMC lineage. My mentor, Dr. Shuo Lin, is an co-PI for 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.
