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 exam ple has been found in which structurally and functionally related genes con trol sex determination in different phyla: the sexual regulators mab-3 of C aenorhabditis elegans and doublesex of Drosophila both encode proteins cont aining the DM domain, a novel DNA-binding motif. These two genes control si milar aspects of sexual development, and the male isoform of DSX can substi tute for MAB-3 in vivo, suggesting that the two proteins are functionally r elated. DM domain proteins may also play a role in sexual development of ve rtebrates. A human gene encoding a DM domain protein, DMRT1, is expressed o nly in the testis in adults and maps to distal 9p24.3, a short interval tha t is required for testis development. Earlier in development we find that m urine 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 b e expressed exclusively in the mammalian genital ridge prior to sexual diff erentiation. Expression becomes XY-specific and restricted to the seminifer ous 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 d evelopment. In birds the heterogametic sex is female (ZW), and the homogame tic sex is male (ZZ). Dmrt1 is Z-linked in the chicken. We find that chicke n 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 theref ore that DM domain genes may play a role in sexual development in a wide ra nge of phyla. (C) 1999 Academic Press.