David Zarkower

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Credentials

PhD

Research Summary

Sexual development is the process that establishes whether an embryo will become male or female. Sex determination and the resulting sexual differentiation are fundamental aspects of normal development, and they profoundly shape the anatomy, physiology, and behavior of nearly all animal species. Moreover, disorders of sexual differentiation (DSDs) are among the most common congenital syndromes and often have serious medical and social consequences. Research in the Zarkower laboratory from 1995 to 2022 sought to uncover molecular and genetic mechanisms that underlie sexual development. We studied several animals, including the nematodes, with their speedy genetics and molecular genetics, mice, where powerful genetic, genomic, and molecular approaches are possible and much of the biology is similar to that of humans, and geckos, which have undergone particularly rapid evolution of sex determination. Much of our work focused on a family of genes we first found in C. elegans, the so-called DM domain transcription factor genes. Two discoveries particularly stood out. First, we found that DM domain genes are widely conserved regulators of sexual development across metazoan animals. Second, we found that the sexual identify of cells in the mammalian gonad has to be actively maintained by DMRT1 and other genes, even in adults, and that disrupting this maintenance can cause cells to “switch” sex through a process of sexual cell fate reprogramming, or sexual transdifferentiation. The DM domain genes also provided many insights into germ line stem cells, control of the mitosis/meiosis switch, sex-specific nervous system development and other important aspects of reproductive biology.