Sexually dimorphic expression of multiple doublesex-related genes in the embryonic mouse gonad

The only molecular similarity shown so far for sexual regulatory genes among different phyla involves doublesex (dsx) of Drosophila, mab-3 and mab-23 of Caenorhabditis elegans, and Dmrt1 of vertebrates. These genes encode DM domain transcription factors (DM = dsx and mab-3) and are required for sexual differentiation. In the case of dsx and mab-3, the two genes control analogous aspects of sexual development, bind similar DNA sequences, and are capable of functional substitution in vivo. All three phyla have multiple DM domain genes, but it is unknown how many of these are involved in sexual development. Mammals, for example, have at least seven DM domain genes, but embryonic expression has only been examined in detail for Dmrt1(dsx- and mab-3 related transcription factor 1). We have identified additional murine DM domain genes and have examined their expression in the mouse embryo, with emphasis on the developing gonad. At least three murine DM domain genes in addition to Dmrt1 are expressed in the embryonic gonad: Dmrt4 is expressed at similar levels in gonads of both sexes; Dmrt3 is more highly expressed in males; and Dmrt7 is more highly expressed in females. Expression of three other genes is low or absent in the embryonic gonad. Two of these, Dmrt5 and Dmrt6, are expressed primarily in the brain, and the third, Dmrt2, is expressed in presomitic mesoderm and developing somites. Our data suggest that multiple DM domain genes may be involved in mammalian sexual development, and that they may function in both testis and ovary development.