The Gonadal Supporting Cell Lineage and Mammalian Sex Determination: The Differentiation of Sertoli and Granulosa Cells.

The supporting cell lineage plays a crucial role in nurturing the development of germ cells in the adult gonad. Sertoli cells in the testis support the progression of spermatogonial stem cells through meiosis to the production of motile spermatozoa. Granulosa cells, meanwhile, are a critical component of the ovarian follicle that produces the mature oocyte. It is a distinctive feature of the embryonic gonad that at least some of the supporting cells are derived from a single sexually bipotential precursor lineage. It is the commitment of this somatic lineage to either the Sertoli or granulosa cell fate that defines sex determination. In this chapter we review what is known about the key molecules responsible for this lineage decision in the developing mammalian gonads, relying primarily on data from studies of mice and humans. We focus on recent advances in our understanding of the mutually antagonistic interactions of testis- and ovary-determining pathways and their complexity as revealed by genetic analyses. For the sake of simplicity, we will deal with supporting cells in testis and ovary development in separate sections, but numerous points of contact exist between these accounts of gonadogenesis in male and female embryos, primarily due to the aforementioned mutual antagonisms. The final section will offer a brief synthesis of these organ-specific overviews and a summary of the key themes that emerge in this review of supporting cell differentiation in mammalian sex determination.