Sex-determining mechanisms are highly variable between phyla. Only one example has been found in which structurally and functionally related genes control sex determination in different phyla: the sexual regulators mab-3 of Caenorhabditis elegans and doublesex of Drosophila both encode proteins containing the DM domain, a novel DNA-binding motif. These two genes control similar aspects of sexual development, and the male isoform of DSX can substitute for MAB-3 in vivo, suggesting that the two proteins are functionally related. DM domain proteins may also play a role in sexual development of vertebrates. A human gene encoding a DM domain protein, DMRT1, is expressed only in the testis in adults and maps to distal 9p24.3, a short interval that is required for testis development. Earlier in development we find that murine 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 be expressed exclusively in the mammalian genital ridge prior to sexual differentiation. Expression becomes XY-specific and restricted to the seminiferous 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 development. In birds the heterogametic sex is female (ZW), and the homogametic sex is male (ZZ). Dmrt1 is Z-linked in the chicken. We find that chicken 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 therefore that DM domain genes may play a role in sexual development in a wide range of phyla.
Deletion of the distal short arm of chromosome 9 (9p) has been reported in a number of cases to be associated with gonadal dysgenesis and XY sex reversal, suggesting that this region contains one or more genes required in two copies for normal testis development. Recent studies have greatly narrowed the interval containing this putative autosomal testis-determining gene(s) to the distal portion of 9p24.3. We previously identified DMRT1, a human gene with sequence similarity to genes that regulate the sexual development of nematodes and insects. These genes contain a novel DNA-binding domain, which we named the DM domain. DMRT1 maps to 9p24. 3 and in adults is expressed specifically in the testis. We have investigated the possible role of DM domain genes in 9p sex reversal. We identified a second DM domain gene, DMRT2, which also maps to 9p24.3. We found that point mutations in the coding region of DMRT1 and the DM domain of DMRT2 are not frequent in XY females. We showed by fluorescence in situ hybridization analysis that both genes are deleted in the smallest reported sex-reversing 9p deletion, suggesting that gonadal dysgenesis in 9p-deleted individuals might be due to combined hemizygosity of DMRT1 and DMRT2.
Vertebrates employ varied strategies, both chromosomal and nonchromosomal, to determine the sex of the developing embryo. Among reptiles, temperature-dependent sex determination (TSD) is common. The temperature of incubation during a critical period preceding sexual differentiation determines the future sex of the embryo, presumably by altering the activity or expression of a temperature-dependent regulatory factor(s). Here we examine the expression of the Dmrt1 gene, a candidate regulator of mammalian and avian sexual development, in the turtle. During the sex-determining period, Dmrt1 mRNA is more abundant in genital ridge/mesonephros complexes at male-promoting than at female-promoting temperatures. Dmrt1 is the first gene found to show temperature-dependent expression prior to sexual differentiation, and may play a key role in sexual development in reptiles. genesis 26:174-178, 2000.
Dmrt2 is expressed in the dermomyotome of developing vertebrate somites. To determine the role of Dmrt2 during mouse embryonic development, we generated a null mutation of Dmrt2 via homologous recombination in embryonic stem cells. Dmrt2 heterozygous mice derived from these cells are phenotypically normal. However, Dmrt2 homozygotes die soon after birth. The cause of death is likely due to abnormal rib and sternal development, leading to an inability to breathe. Loss of Dmrt2 leads to embryonic somite patterning defects, first evidenced at embryonic day (E) 10.5 and more pronounced by E11.5. Notably, both the dermomyotome and myotome fail to adopt a normal epithelial morphology in the absence of Dmrt2. Accompanying these morphological defects are alterations in the expression patterns of dermomyotomal and myotomal transcription factors including Pax3, Paraxis, Myf5, myogenin, Mrf4 and MyoD. Despite these defects, embryos harvested from E13.5 onwards exhibited relatively normal muscle pattern and mass, suggesting that early myotomal defects are corrected by a Dmrt2-independent mechanism. Taken together, our results define an essential function for Dmrt2 in somite development and provide evidence that DM domain genes have been co-opted into other critical developmental pathways distinct from that of sex determination or differentiation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.