Slugs and snails, or sugar and spice?: Sex determination and sexual differentiation

Mammalian existence relies upon pregnancy producing either male or female offspring. Under normal circumstances, this ‘polarized’ outcome is determined by the chromosomal constitution of the spermatozoan that successfully fertilizes the ovum -- a Y chromosome acts dominantly to produce a male foetus. This concept of sex chromosome action has been with us for almost a century1. However, understanding the genetic steps between fertilization and the development of male or female appearance proved less forthcoming for a long time. Building upon the landmark experiments of Jost in the 1940s2, the previous decade has witnessed significant advances in the understanding of male and female development3. For the most part, information has arisen either by genetic manipulation of laboratory mice or by careful clinical and molecular genetic analyses of human individuals with sex reversal. In both circumstances, chromosomal constitution (46,XY or 46,XX) fails to correspond to the sexual phenotype (male or female).