During mammalian sex-determination, Sox9 is expressed in males shortly after Sry, the master regulator of mammalian sex-determination. In humans, heterozygous SOX9 loss-of-function mutations underlie campomelic dysplasia, which, as well as other defects, can cause abnormal testicular differentiation or even complete sex reversal in XY individuals. Previous studies have shown that Sox9 is sufficient to induce testis formation but, on p. 1891, Chaboissier et al. use conditional gene targeting in the mouse gonad to show, for the first time, that Sox9 is necessary, as well as sufficient, for mediating the switch from the ovarian to the testicular pathway. The authors also found that Sox9 is essential for normal Sertoli cell differentiation and seminiferous tubule formation. Finally, they demonstrate that the closely related protein Sox8 reinforces Sox9 function in mouse testis differentiation, and suggest that this could explain the incomplete penetrance of sex-reversal in XY SOX9 heterozygous individuals.

© 2004.
2004