Expression of FoxL2 in the murine ovary: a forkhead protein implicated in premature ovarian failure

Abstract

The exact mechanism propelling primordial ovarian follicles to emerge from the resting pool and resume development remains elusive. Furthermore, a vague understanding of the molecular interaction between germ and somatic cells during primordial follicle formation currently exists. As such, some novel insights into ovarian follicular development have been realized through the study of relevant knockout mouse models. More precisely, targeted disruption of the winged-helix/ forkhead domain transcription factor, FoxL2, has indicated it to be essential in differentiation and development of granulosa cells and all major somatic cell lineages surrounding growing oocytes from the onset of primordial follicle formation. In this regard, I have identified both murine FoxL2 mRNA and protein to be highly granulosa cell specific in the adult animal and that the onset of this expression occurs at the critical transition from the primordial into the primary stage of follicular development. Next, the exact of mechanism of FoxL2 regulation is yet poorly defined. However, FoxL2 has been shown to directly interact with Smad3, signaling mediator of the TGF-β family of growth and differentiation factors. With this in mind, I confirmed the presence of BMPRII in our FoxL2 expressing granulosa cell model, identified as a functional receptor for TGF-β signaling specifically mediated by Smads 2 and 3. At issue, then, was the identity of a suitable ligand capable of regulating FoxL2 expression. Toward this end, my studies have characterized FoxL2 as perhaps exhibiting an internuclear rather than intercellular redistribution event in contrast to the nucleocytoplasmic shuttling typifying related forkhead family members. I specifically noted the presumed internuclear reorganization of FoxL2 in response to forskolin (PKA mediated) induced stimulation. However, the functional implication of the resultant reorganization of FoxL2 in the nucleus remains to be seen. Upon doing so, I might better be able to forge a connection between the observed internuclear activity of FoxL2 and the differential expression of specific genetic markers that I have conveyed as the outcome of FoxL2 cDNA microarray analysis.