Genes essential for early events in gonadal development

The acquisition of a sexually dimorphic phenotype is a key event in mammalian development. The underlying principle of this essential process is that genetic sex, determined by the presence or absence of a Y chromosome at fertilization, directs the embryonic gonads to differentiate into either testes or ovaries. Hormones produced by the testes then trigger the developmental program that leads to male phenotypic sexual differentiation. Without testes and their biochemical products, differentiation proceeds along the female pathway. Recent studies have identified several transcription factors that are required for gonadal development and sexual differentiation, i.e. Wilms' tumor related 1 (WT1), steroidogenic factor 1 (SF-1), SOX9, and GATA4, presumably because they activate the expression of essential target genes. Studies also have identified another transcriptional regulator, designated DAX-1, that inhibits target gene induction by all of these transcriptional activators. This chapter provides an overview of gonadal development and sexual differentiation, reviews the studies that have led to the isolation and characterization of these genes in the gonads, and then discusses how they interact to regulate critical events in sexual differentiation.