Sex determination is governed by a series of genetic switches that influence cell fate and differentiation during critical periods of gonadal development. Remarkably, the primordial fetal gonad is bipotential. Therefore, gonadal development provides an excellent opportunity to identify genes involved in differential organogenesis. The identification of the testis-determining gene, SRY (Sex-reversed on the Y), was a pivotal first step towards unraveling this genetic pathway. It is now clear that numerous other genes, in addition to SRY, are necessary for normal testis development. For example, human mutations in a variety of genes (SOX9, WT1, SF1) impair testis development. Murine models provide evidence for additional genes (Lhx9, Emx2, M33, Dmrt, Fgf9). This lecture will highlight insights gleaned from human mutations in the nuclear receptors, SF1 (Steroidogenic Factor1) (NR5A1) and DAX1 (Dosage-sensitive sex reversal, Adrenal hypoplasia congenita, X chromosome) (NR0B1). These studies reveal the exquisite sensitivity of SF1-dependent developmental pathways to gene dosage and function in humans.
|Original language||English (US)|
|Pages (from-to)||51-63; discussion 64-65|
|Journal||Transactions of the American Clinical and Climatological Association|
|State||Published - 2003|
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