I-51: The Role of the Transcription FactorGCNF in Germ Cell Differentiation and Reproductionin Mice

The germ cell nuclear factor (GCNF) is a member of the nuclear receptor super family of transcription factors. GCNF expression during gastrulation and neurulation is critical for normal embryogenesis in mice. GCNF represses expression of the POU domain transcription factor Oct4 during mouse post-implantation development in vivo. Oct4 is thus down-regulated during female gonadal development, when the germ cells enter meiosis, which is a process important for reproduction,but one that is rare in germ cells derived from embryonic stem cells in vitro. One aim of our work is to better define the role of GCNF during mouse germ cell development in vivo. We observed a steady decrease in pluripotency-associated gene activity with a concomitant up-regulation of GCNF expression in germ cells derived from developing fetal gonads one day prior to the onset of meiosis. Meiosis-associated genes were then upregulated at onset of meiosis. These findings suggests that GCNF may repress Oct4 expression in female germ cells and that it plays a role in initiation of meiosis or in activation of meiosis-associated genes in female germ cells. To further investigate the role of GCNF in meiotic processes in male germ cells we generated a GCNF knock-down model to monitor the effect of GCNF during spermatogenesis in a functional manner. The ultimate goal of our studies is to better understand key mechanisms during germ cell development that will serve the in vitro derivation of healthy and functional gametes.