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Primary Sex Determination
The gonad, which arises as a bipotential primordium, is an ideal model system for studying the processes of cell fate determination and organogenesis. The primary step in sex determination is the decision that occurs within the bipotential gonad to differentiate as a testis or ovary. This decision guides subsequent sexual differentiation throughout the embryo. Underlying this decision is a complex transcriptional network composed of male and female sub-networks that act in an antagonistic manner to balance the gonad between its alternate fates. In XX gonads, the female sub-network dominates and represses the male pathway. However, expression of the Y-linked male sex-determining gene, Sry, tips the balance in XY gonads in favor of the male pathway, which leads to the organization and differentiation of gonadal cells into a testis. We have employed a genetic systems level approach to investigate the dynamics of the transcriptome underlying the cell fate decision in gonadal cells. We have determined the origin of several key cell types of the testis, and identified a number of pathways that lead to the architectural patterning of the testis and ovary. We are currently particularly interested in early steps in the establishment of the gonad primordium, and in how the decision to commit to testis or ovary fate is propagated across the field of cells. We have recently sequenced the gonad transcriptome in the red-eared slider turtle, where sex is determined by the incubation temperature of the egg rather than by a sex chromosome difference. We are very interested in determining whether there are underlying similarities in the dynamic transcriptional network between mice and turtles, and we would like to understand how temperature intersects with gene expression to control sexual fate. Finally, we investigate how interactions with the somatic cells of the gonad regulate the latent totipotency of germ cells and control their differentiation as oogonia or spermatogonia. Experimental approaches include the use of molecular and biochemical techniques, advanced imaging methods, null mutant mice, transgenic reporter mice, organ culture/tissue recombination assays, mouse genetics and genomics, and systems biology.
Listen to Blanche giving radio interviews about sex determination
NPR “Morning Edition”: Half-Rooster/Half-Hen Helps Unlock Sex Mystery