SOX E genes: SOX9 and SOX8 in mammalian testis development

Abstract

The group E SOX proteins consist of SOX8, SOX9 and SOX10. These transcription factors contain, besides a DNA-binding HMG domain and a transactivation domain, a DNA-dependent dimerization domain, unique among SOX proteins. Among these three SOX E proteins, which are all expressed during mammalian testis development, SOX9 stands out in importance. It is SOX9 that becomes activated by SRY in pre-Sertoli cells, executing SRY's role as a testis-determining factor by inducing Sertoli cell and testis cord differentiation. However, Sox9 is dispensable during subsequent embryonic and postnatal testis development, since ablation of Sox9 at embryonic day 14.0, after the sex determination stage, only leads to late-onset sterility at about 5 months. A similar late male sterility phenotype occurs in constitutive Sox8 null mutants. In the combined absence of Sox9 and Sox8, primary male infertility evolves, revealing functional redundancy. Loss of Sox10 has no effect on testis development.