DMRT1/Dmrt1, the Sex Determining or Sex Differentiating Gene in Vertebrata

Although the phenomenon of sexual dimorphism is widespread in vertebrates, the molecular mechanism of sex-determination is not the same across animal phyla, in contrast to other areas of developmental biology. Recent extensive studies, however, have given proof of evolutionarily conserved function in genes which share a novel DNA binding DM domain, primarily identified in two invertebrate sex regulatory genes: doublesex of Drosophila melanogaster and mab-3 of Caenorhabditis elegans. Their mammalian autosomal homologue, DMRT1, first isolated in humans, was further discovered in genomes of various vertebrate species and appears to be involved in similar aspects of sexual development. Its precise role is still speculated, thus identification of sex reversal mutations, functional studies as well as determination of the sex-specific expression profile during embryogenesis are still being undertaken. Is this a sex determining rather than a sex differentiating gene? Is it involved in a dosage-sensitive mechanism? On what level does it function in the hierarchy of the sexual regulatory gene cascade? Recent results are discussed in this paper.