LAUSR

The current proposal aims to investigate the mechanisms by which two steroids, pregnenolone (P5) and progesterone (P4) affect zebrafish embryo development. We showed that pregnenolone promoted cell migration, while progesterone was involved in cell patterning. We are also studying the effect of progesterone on embryo patterning by disrupting the gene involved in P4 biosynthesis, hsd3b2. Disruption of hsd3b2 resulted in embryo dorsalization by decreasing zebrafish bmp4 transcription.We identified a progesterone-responsive element located in the enhancer of hsd3b2, which could bind to progesterone receptor (Pgr) and mediate the effect of P4 in regulating bmp4 expression. Depletion of pgr resulted in the samedorsalization phenotype as hsd3b2 morphants. Thus, we showed that hsd3b2 is involved in the synthesis of P4, which activated bmp4 transcription during the early epiboly stage of embryogenesis, thus setting up Bmp4 gradient important for the development of ventral tissues. The studies described above should provide insights into the novel functions of P4 and P5 both in zebrafish embryogenesis and in the mammalian system. Microtubule dynamics and cell migration is very important in several cellular processes; and their disturbances have been described in many diseases. The elucidation of the mechanism by which small compounds like P5 regulate microtubule dynamics will be very important.