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Sex and the singular DM domain: insights into sexual regulation, evolution and plasticity

Key Points

  • Most animals reproduce sexually and thus require a sex-determining mechanism.

  • Sex-determining mechanisms are surprisingly diverse among animal species, and genes at the top of sex-determining pathways rapidly turn over during evolution.

  • Genes containing the DM domain DNA-binding motif appear to have an ancient and conserved role in controlling sexual differentiation and sex determination.

  • Invertebrate DM domain genes integrate spatial and temporal inputs with sex-determining pathways to coordinate the sexual differentiation of diverse structures.

  • Studies of the DM domain gene doublesex in Drosophila melanogaster are revealing how new sexually dimorphic features evolve.

  • In vertebrates, the DM domain gene Dmrt1 is required for testicular development.

  • In several non-mammalian vertebrates (that is, birds, fish and amphibians) Dmrt1 or a close homologue has acquired control of sex determination during evolution.

  • Detailed studies in the mouse reveal that Dmrt1 has diverse functions in gonadal development, including a role in preventing male-to-female transdifferentiation of testis cells.

Abstract

Most animals reproduce sexually, but the genetic and molecular mechanisms that determine the eventual sex of each embryo vary remarkably. DM domain genes, which are related to the insect gene doublesex, are integral to sexual development and its evolution in many metazoans. Recent studies of DM domain genes reveal mechanisms by which new sexual dimorphisms have evolved in invertebrates and show that one gene, Dmrt1, was central to multiple evolutionary transitions between sex-determining mechanisms in vertebrates. In addition, Dmrt1 coordinates a surprising array of distinct cell fate decisions in the mammalian gonad and even guards against transdifferentiation of male cells into female cells in the adult testis.

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Figure 1: DM domain genes in metazoan sexual development.
Figure 2: Diverse roles of DMRT1 orthologues in vertebrate sex determination.

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Acknowledgements

The authors thank T. Gamble for assistance with figures, the anonymous reviewers for helpful comments on the manuscript and the US National Institutes of Health and US National Science Foundation for financial support.

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Correspondence to David Zarkower.

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Glossary

Spicules

A pair of sensory and copulatory structures in the male tail that are used to help anchor the male to the hermaphrodite vulva during mating.

Oenocytes

Clustered secretory cells found under the abdominal epidermis in insects.

Dysgenetic gonads

Gonads that have developed abnormally but have not undergone a full sexual transformation.

Seminomas

Malignant testicular germ cell tumours of uniform cell composition.

Nonseminomas

Malignant testicular germ cell tumours composed of mixed cell types

Gynandromorphs

Organisms that contain a mixture of male and female cells. Gynandromorphs can be bilateral (male on one side and female on the other) or mosaic (a random mixture of male and female cells).

Leydig cells

Secretory cells that produce testosterone and are found adjacent to the seminiferous tubules of the testis.

Induced pluripotent stem cells

(iPSCs). Pluripotent stem cells that are artificially derived from non-pluripotent cells, typically by genetic manipulation.

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Matson, C., Zarkower, D. Sex and the singular DM domain: insights into sexual regulation, evolution and plasticity. Nat Rev Genet 13, 163–174 (2012). https://doi.org/10.1038/nrg3161

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