Chapter 7. Conclusions

The present results demonstrate a role for Wnt-4 in female development. It is expressed in a sexually dimorphic manner in the developing urogenital system, in the gonads of both sexes at first but only in the developing ovary after sex determination while its expression in the Müllerian duct and adrenal gland is independent of sex. The lack of Wnt-4 leads to partial female-to-male sex reversal, which is the first female sex reversal to be identified, as all the other reported cases are male-to-female changes. In addition, Wnt-4 is needed for Müllerian duct development in both sexes. Absence of the Müllerian duct admittedly has no essential consequences in males, but in females the oviduct, uterus and upper part of the vagina will not form. Furthermore, the lack of Wnt-4 leads to a dramatic reduction in the number of oocytes, indicating that it is needed either for the survival of the oocyte itself or for the development of the supporting cells.

Wnt-4 also plays a role in adrenal gland development. The number of cells producing aldosterone is reduced in Wnt-4 mutant mice, and as aldosterone is produced only within the zona glomerulosa, this layer evidently does not develop normally in Wnt-4 mutant mice.

Wnt-4 is the first signalling factor to be identified as playing a role in mammalian sex determination and in the female developmental pathway. Identification of its essential function allows the researcher to set out on a search for the molecular mechanisms, which control female sex determination.

The conditional Wnt-4 knock-out mouse model should enable the precise roles of Wnt-4 in specific tissue types to be determined at some time in the future.