DMY is a Y-specific DM-domain gene required for male development in the medaka fish

Abstract

Although the sex-determining gene Sry has been identified in mammals, no comparable genes have been found in non-mammalian vertebrates. Here, we used recombinant breakpoint analysis to restrict the sex-determining region in medaka fish (Oryzias latipes) to a 530-kilobase (kb) stretch of the Y chromosome. Deletion analysis of the Y chromosome of a congenic XY female further shortened the region to 250 kb. Shotgun sequencing of this region predicted 27 genes. Three of these genes were expressed during sexual differentiation. However, only the DM-related PG17 was Y specific; we thus named it DMY. Two naturally occurring mutations establish DMY's critical role in male development. The first heritable mutant--a single insertion in exon 3 and the subsequent truncation of DMY--resulted in all XY female offspring. Similarly, the second XY mutant female showed reduced DMY expression with a high proportion of XY female offspring. During normal development, DMY is expressed only in somatic cells of XY gonads. These findings strongly suggest that the sex-specific DMY is required for testicular development and is a prime candidate for the medaka sex-determining gene.

Sexual dimorphic expression of DMRT1 and Sox9a during gonadal differentiation and hormone‐induced sex reversal in the teleost fish Nile tilapia (Oreochromis niloticus)

“…Unfortunately, in teleost fish, the expression profiles of DMRT1 compared with those of morphological sexual dimorphisms in terms of germ cell number and histogenesis have not been reported in any species except for medaka (Kobayashi et al, 2004). In medaka (Oryzias latipes), the sex-determining gene DMY has been identified, and this gene is a DMRT1 homolog (Matsuda et al, 2002(Matsuda et al, , 2003. Also, DMY is found in two subspecies of medaka (Matsuda et al, 2003), but in no other medaka species.…”

Genetic basis of male sexual behavior

“…These genes are members of the DM-domain transcription factor family and are required for multiple diverse aspects of male development in worms, flies, and vertebrates (Raymond et al, 1998(Raymond et al, , 2000Zarkower, 2001;Matsuda et al, 2002). Their conservation across phyla in both structure and function is in contrast to the nonconservation of genes upstream of them in the sex-determination hierarchy (Hodgkin, 1992;Wilkins, 1995;Marín and Baker, 1998).…”

“…Deletion of a mouse member of the family (DMRT1) resulted in abnormal testes development (Raymond et al, 2000), and deletion of a region of chromosome 9 containing a cluster of DM genes resulted in sex-reversal (Ottolenghi et al, 2002). In medaka fish, a DM-domain gene closely related to DMRT1 plays a primary role in sex determination (Matsuda et al, 2002). Given the hormonal mode of vertebrate development, in which development of the soma appears to be entirely dependent on the sex of the gonad, it is unclear whether these genes will be found to play any direct role in differentiation of the vertebrate nervous system.…”

Germline stem cells are critical for sexual fate decision of germ cells

“…However, contrary to the initial prediction that Sry is conserved among vertebrates, many animals do not possess an Sry homolog. Ten years after the discovery of Sry , DMY / Dmrt1bY was identified as the sex determination gene on the sex chromosome in the teleost fish, medaka 5, 6. Since this discovery, other sex determination genes have also been identified in various vertebrates.…”

“…All sex determination genes examined thus far are expressed in the somatic (supporting) cells that directly surround the germ cells in the gonad 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. Therefore, it is reasonable to speculate that the sexual fate of germ cells (in other words, the fate decision of germ cells to develop eggs or sperms) is triggered by the sex of the surrounding somatic cells during a normal sex determination process.…”