Biased precursor ingression underlies the center-to-pole pattern of male sex determination in mouse

During mammalian development, gonadal sex determination results from the commitment of bipotential supporting cells to Sertoli or granulosa cell fates. Typically, this decision is coordinated across the gonad to ensure commitment to a single organ fate. When unified commitment fails in an XY mouse, an ovotestis forms in which supporting cells in the center of the gonad typically develop as Sertoli cells, while supporting cells in the poles develop as granulosa cells. This central bias for Sertoli cell fate was thought to result from the initial expression of the drivers of Sertoli cell fate, SRY and/or SOX9, in the central domain, followed by paracrine expansion to the poles. However, we show here that the earliest cells expressing SRY and SOX9 are widely distributed across the gonad. In addition, Sertoli cell fate does not spread among supporting cells through paracrine relay. Instead, we uncover a center-biased pattern of supporting cell precursor ingression that occurs in both sexes and results in increased supporting cell density in the central domain. Our findings prompt a new model of gonad patterning in which a density-dependent organizing principle dominates Sertoli cell fate stabilization.

Automated summary

During mammalian development, the commitment of bipotential supporting cells to Sertoli or granulosa cell fates plays a crucial role in gonadal sex determination. In XY mice, failure of unified commitment leads to the formation of an ovotestis, where central supporting cells develop as Sertoli cells while pole supporting cells develop as granulosa cells. However, contrary to previous beliefs, the expression of SRY and SOX9, the drivers of Sertoli cell fate, is not limited to the central domain and Sertoli cell fate is not spread through paracrine relay among supporting cells. Instead, there is a center-biased pattern of supporting cell precursor ingression, resulting in increased supporting cell density in the central domain.