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SRY and the Standoff in Sex Determination

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710

Address all correspondence and requests for reprints to: Dr. Blanche Capel, Box 3709, Nanaline Duke, Research Drive, Duke University Medical Center, Durham, North Carolina 27710. E-mail: b.capel{at}cellbio.duke.edu.

SRY was identified as the mammalian sex-determining gene more than 15 yr ago and has been extensively studied since. Although many of the pathways regulating sexual differentiation have been elucidated, direct downstream targets of SRY are still unclear, making a top down approach difficult. However, recent work has demonstrated that the fate of the gonad is actively contested by both male-promoting and female-promoting signals. Sox9 and Fgf9 push gonads towards testis differentiation. These two genes are opposed by Wnt4, and possibly RSPO1, which push gonads toward ovary differentiation. In this review, we will discuss the history of the field, current findings, and exciting new directions in vertebrate sex determination.