Mammalian sex determination is a complex business. For example, the sex-determining region on the Y chromosome (Sry) is essential for male genital development, but mutations in other genes can also cause sex reversal. Bouma et al. now present a new model for testicular development in male XY mice (see ) in which the upregulation of Sox9 in Sertoli cell precursors - an essential event for testis development - depends on the expression of correct doses of Sry and Dax1 (an X-linked gene), and of one or more autosomal genes. The authors' genetic, histological and gene expression analyses show, for example, that Dax1, which encodes a nuclear receptor transcription factor, is essential for embryonic testis development in a mouse strain that is particularly susceptible to disturbances of testicular development. Elegant genetic studies also lead the authors to suggest that Wnt4 might be a sex determination modifier locus, called Tda1, that is present on chromosome 4.
