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Expression of Dmrt1 in the genital ridge of mouse and chicken embryos suggests a role in vertebrate sexual development.

Sex-determining mechanisms are highly variable between phyla. Only one example has been found in which structurally and functionally related genes control sex determination in different phyla: the sexual regulators mab-3 of Caenorhabditis elegans and doublesex of Drosophila both encode proteins containing the DM domain, a novel DNA-binding motif. These two genes control similar aspects of sexual development, and the male isoform of DSX can substitute for MAB-3 in vivo, suggesting that the two proteins are functionally related. DM domain proteins may also play a role in sexual development of vertebrates. A human gene encoding a DM domain protein, DMRT1, is expressed only in the testis in adults and maps to distal 9p24.3, a short interval that is required for testis development. Earlier in development we find that murine Dmrt1 mRNA is expressed exclusively in the genital ridge of early XX and XY embryos. Thus Dmrt1 and Sry are the only regulatory genes known to be expressed exclusively in the mammalian genital ridge prior to sexual differentiation. Expression becomes XY-specific and restricted to the seminiferous tubules of the testis as gonadogenesis proceeds, and both Sertoli cells and germ cells express Dmrt1. Dmrt1 may also play a role in avian sexual development. In birds the heterogametic sex is female (ZW), and the homogametic sex is male (ZZ). Dmrt1 is Z-linked in the chicken. We find that chicken Dmrt1 is expressed in the genital ridge and Wolffian duct prior to sexual differentiation and is expressed at higher levels in ZZ than in ZW embryos. Based on sequence, map position, and expression patterns, we suggest that Dmrt1 is likely to play a role in vertebrate sexual development and therefore that DM domain genes may play a role in sexual development in a wide range of phyla.