High impact information on Dmrt1

• Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation [1].
• Such evidence is highly suggestive of a conserved role(s) for Dmrt1 in vertebrate sexual development, but there has been no functional analysis of this gene in any species [1].
• Here we show that murine Dmrt1 is essential for postnatal testis differentiation, with mutant phenotypes similar to those caused by human chromosome 9p deletions that remove the gene [1].
• Of seven mammalian DM domain genes, only Dmrt1 and Dmrt2 have been functionally analyzed [2].
• Gata4 regulates testis expression of Dmrt1 [3].

Biological context of Dmrt1

• Multiple alternative splicing of mouse Dmrt1 during gonadal differentiation [4].
• These results provide new insight into roles of regulation at level of splicing of the Dmrt1 in governing sex differentiation [4].
• Northern blot and real time fluorescent quantitative RT-PCR further indicated that the expression of Dmrt1 a was dominantly higher than those of Dmrt1 b, c, and d, although they showed a similar up and down pattern of expression during embryo development [4].
• Dmrt1, a gene that contains the DM-domain (Doublesex/Mab-3 DNA-binding motif), is considered to be one of the essential genes involved in the testicular differentiation cascade in mammals, birds, reptiles, and fish [5].
• In this study, we have successfully isolated a Dmrt1 homolog from the frog Rana rugosa testes cDNA library and examined its expression during gonadal differentiation and in sex-reversed gonads [5].

Anatomical context of Dmrt1

• 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 [6].
• 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 [6].
• The doublesex and mab-3 related transcription factor 1 (Dmrt1) is a putative transcriptional regulator that is expressed exclusively in the gonads and is required for postnatal testis differentiation [3].
• The Dmrt1 was first expressed in the differentiating testis at stage XXV in which spermatogonia are only germ cells, and became stronger at later stages [5].
• In addition, the Dmrt1 mRNA was first detected in the gonad/mesonephros complex of tadpoles at stage 53, at which time the gonads were still indifferent [7].

Other interactions of Dmrt1

• Further transient-transfection assays of various mutant promoters established the functional relevance of the Gata4-response and unknown factor-response elements, while studies of Dmrt1 expression in 13.5 days postcoitum Fog2 null gonads supported the in vivo importance of Gata4's regulation [3].

Analytical, diagnostic and therapeutic context of Dmrt1

• RT-PCR showed that all of Dmrt1 transcripts were only detectable in adult testis [4].
• To elucidate its role(s) for gonadal differentiation in vertebrates, a molecular cloning of Dmrt1 in amphibians is urgent [5].
• Site-directed mutagenesis of these regions identified 2 elements that activate the Dmrt1 promoter and 2 that repress it [8].

References