Sex determination and SRY: down to a wink and a nudge?

Sex-determining region Y (Sry) is the crucial gene that initiates male sex determination in most mammals. Although several components of the pathway regulating sexual differentiation have been elucidated, the mechanism of Sry action within this was unclear. However, recent discoveries in cellular, genetic and molecular aspects of gonad development are shedding light on the precise role of SRY in the regulation of Sox9, a crucial downstream target gene. SRY is thought to act synergistically with SF1, a nuclear receptor, through an enhancer of Sox9 to promote Sertoli cell differentiation in mice. In this review, we focus on the regulation of these genes and their interaction with other genes involved in promoting testis or ovary development. We also explore the common features between sex determination in mammals and in other vertebrates that lack Sry.