Invertebrates may not be so different after all

Sex determination is widespread, but uses highly varied molecular mechanisms. A possible case of conservation between phyla is that of doublesex (dsx) from Drosophila and mab-3 (male abnormal 3) from Caenorhabditis elegans, genes related in sequence and some elements of function. mab-3 controls multiple aspects of male development, including sense organ formation in the tail and yolk transcription in the intestine, both similar to functions of dsx. Indeed, the male isoform of DSX can replace MAB-3 in C. elegans. Do related genes control sexual development in vertebrates, despite great differences in the biology of sex determination? We have identified several dsx-related genes in mouse and human. One, Dmrt1, appears to play a conserved role in vertebrate male gonad development. In humans, DMRT1 maps to a short interval required for testis differentiation. In all vertebrates examined, including mammals, birds, fish, and reptiles, Dmrt1 is expressed early in the genital ridge, in most cases with higher expression in future male gonads. A null mutation in murine Dmrt1 causes severe defects in testis differentiation, resembling those associated with human deletions removing the gene. Mutant females are unaffected. Other DM domain genes are expressed in embryonic gonad and are currently under study.