Development of the Mammalian Gonad: Key Sex‐Determining Genes in Mice and Humans

Abstract

Abstract Sex determination is the process by which an embryo commits to the male or female gonadal fate. Our understanding of mammalian sex determination is dominated by the consideration of data from humans and mouse models. Humans and mice share important elements of their reproductive biology, and therefore experimentation in the mouse offers the prospect of detailed mechanistic insights into typical and atypical human sexual development. Recent studies reveal a high degree of conservation in the roles played by sex‐determining genes in mice and humans, but also important differences. Key themes that have emerged from mouse genetics studies include the mutually antagonistic roles of testis‐ and ovary‐determining genes and the requirement to maintain these long after the primary sex‐determining event. The advent of technologies such as next‐generation sequencing and genome editing promises to shed more light on the causes of disorders of sex development in humans, as well as fundamental mechanisms in cell fate commitment in the mammalian gonad. Key Concepts The mammalian gonad (testis or ovary) develops from a bipotential primordium in which genes associated with later sexual differentiation are expressed. The testis‐ and ovary‐determining gene networks are mutually antagonistic during primary sex determination. The maintenance of cell identity in the differentiated adult gonad requires continued inhibition of opposing genetic pathways. Interpreting the nature of mutations associated with human genetic disease, including disorders of sex development (DSD), is aided by the generation and study of mouse models.