Sex Determination, Human

Abstract

The critical event in human sex determination is whether the embryonic undifferentiated gonad develops as a testis or an ovary. The formation and maintenance of the undifferentiated gonad requires the concerted action of numerous genes such as SF1/NRA5A1, WT1, LIM1, LHX9, EMX2, and CBX2. If the embryo has an XY sex chromosome constitution, then the Y-linked SRY gene initiates a developmental network of genes (SOX9, FGF9, DHH, DMRT1, AMH, DAX1/NROB1, and SF1/NRA5A1) that results in a functional testis. By contrast, in an XX embryo the undifferentiated gonad develops as an ovary under the active developmental regulation of genes such as WNT4, RSPO1, β-catenin, and FOXL2. Perturbation of any of..