Sex in the 90s: SRY and the switch to the male pathway

Abstract

In mammals the male sex determination switch is controlled by a single gene on the Y chromosome, SRY. SRY encodes a protein with an HMG-like DNA-binding domain, which probably acts as a local organizer of chromatin structure. It is believed to regulate downstream genes in the sex determination cascade, although no direct targets of SRY are clearly known. More genes in the pathway have been isolated through mutation approaches in mouse and human. At least three genes, SRY itself, SOX9, and DAX1, are dosage sensitive, providing molecular evidence that the sex determination step operates at a critical threshold. SRY initiates development of a testis from the bipotential cells of the early gonad. The dimorphic male and female pathways present a rare opportunity to link a pivotal gene in development with morphogenetic mechanisms that operate to pattern an organ and the differentiation of its cells. Mechanisms of testis organogenesis triggered downstream of SRY include pathways of cell signaling controlling cell reorganization, cell proliferation, cell migration, and vascularization.