Dmrt1

Summary

Gene Symbol: Dmrt1
Description: doublesex and mab-3 related transcription factor 1
Alias: doublesex- and mab-3-related transcription factor 1
Species: mouse
Products:     Dmrt1

Top Publications

  1. Manuylov N, Zhou B, Ma Q, Fox S, Pu W, Tevosian S. Conditional ablation of Gata4 and Fog2 genes in mice reveals their distinct roles in mammalian sexual differentiation. Dev Biol. 2011;353:229-41 pubmed publisher
    ..We have established that GATA4 is required for testis differentiation, for the expression of Dmrt1 gene, and for testis cord morphogenesis...
  2. Smith C, McClive P, Western P, Reed K, Sinclair A. Conservation of a sex-determining gene. Nature. 1999;402:601-2 pubmed publisher
  3. Kim S, Bardwell V, Zarkower D. Cell type-autonomous and non-autonomous requirements for Dmrt1 in postnatal testis differentiation. Dev Biol. 2007;307:314-27 pubmed
    ..The DM domain gene Dmrt1 is essential for testicular differentiation in vertebrates...
  4. Matson C, Murphy M, Griswold M, Yoshida S, Bardwell V, Zarkower D. The mammalian doublesex homolog DMRT1 is a transcriptional gatekeeper that controls the mitosis versus meiosis decision in male germ cells. Dev Cell. 2010;19:612-24 pubmed publisher
    ..Here we examine the role of the Doublesex-related transcription factor DMRT1 in adult spermatogenesis using conditional gene targeting in the mouse...
  5. Raymond C, Kettlewell J, Hirsch B, Bardwell V, Zarkower D. Expression of Dmrt1 in the genital ridge of mouse and chicken embryos suggests a role in vertebrate sexual development. Dev Biol. 1999;215:208-20 pubmed
    ..A human gene encoding a DM domain protein, DMRT1, is expressed only in the testis in adults and maps to distal 9p24...
  6. Raymond C, Murphy M, O Sullivan M, Bardwell V, Zarkower D. Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev. 2000;14:2587-95 pubmed
    ..A DM domain gene called Dmrt1 has been implicated in male gonad development in a variety of vertebrates, on the basis of embryonic expression ..
  7. Murphy M, Sarver A, Rice D, Hatzi K, Ye K, Melnick A, et al. Genome-wide analysis of DNA binding and transcriptional regulation by the mammalian Doublesex homolog DMRT1 in the juvenile testis. Proc Natl Acad Sci U S A. 2010;107:13360-5 pubmed publisher
    ..One of these proteins, DMRT1, plays diverse and essential roles in development of the vertebrate testis...
  8. Fahrioglu U, Murphy M, Zarkower D, Bardwell V. mRNA expression analysis and the molecular basis of neonatal testis defects in Dmrt1 mutant mice. Sex Dev. 2007;1:42-58 pubmed publisher
    ..b>Dmrt1, 1 of 7 mammalian DM domain genes, is essential for several aspects of testicular differentiation in mice...
  9. Matson C, Murphy M, Sarver A, Griswold M, Bardwell V, Zarkower D. DMRT1 prevents female reprogramming in the postnatal mammalian testis. Nature. 2011;476:101-4 pubmed publisher
    ..Here we show that sexual fate is also surprisingly labile in the testis: loss of the DMRT1 transcription factor in mouse Sertoli cells, even in adults, activates Foxl2 and reprograms Sertoli cells into ..

More Information

Publications51

  1. Murphy M, Zarkower D, Bardwell V. Vertebrate DM domain proteins bind similar DNA sequences and can heterodimerize on DNA. BMC Mol Biol. 2007;8:58 pubmed
    ..No detailed analysis of DNA binding by the seven vertebrate DM domain proteins, DMRT1-DMRT7 has been reported, and thus it is unknown whether they recognize similar or diverse DNA sequences...
  2. Brunner B, Hornung U, Shan Z, Nanda I, Kondo M, Zend Ajusch E, et al. Genomic organization and expression of the doublesex-related gene cluster in vertebrates and detection of putative regulatory regions for DMRT1. Genomics. 2001;77:8-17 pubmed publisher
    ..Evidence has accumulated for the involvement of DMRT1 in male sex determination and differentiation...
  3. Lu H, Huang X, Zhang L, Guo Y, Cheng H, Zhou R. Multiple alternative splicing of mouse Dmrt1 during gonadal differentiation. Biochem Biophys Res Commun. 2007;352:630-4 pubmed
    Evolutionarily conserved Dmrt1 encodes a transcriptional regulator that is expressed exclusively in the gonads and is required for testis differentiation...
  4. Lavery R, Chassot A, Pauper E, Gregoire E, Klopfenstein M, de Rooij D, et al. Testicular differentiation occurs in absence of R-spondin1 and Sox9 in mouse sex reversals. PLoS Genet. 2012;8:e1003170 pubmed publisher
    ..The dogma that considers female differentiation as a default pathway therefore needs to be definitively revised. ..
  5. Guan G, Kobayashi T, Nagahama Y. Sexually dimorphic expression of two types of DM (Doublesex/Mab-3)-domain genes in a teleost fish, the Tilapia (Oreochromis niloticus). Biochem Biophys Res Commun. 2000;272:662-6 pubmed publisher
    ..Vertebrate DMRT1 (DM-related transcription factor 1) expression occurs predominantly in testis...
  6. Zhang L, Lu H, Xin D, Cheng H, Zhou R. A novel ncRNA gene from mouse chromosome 5 trans-splices with Dmrt1 on chromosome 19. Biochem Biophys Res Commun. 2010;400:696-700 pubmed publisher
    b>Dmrt1 (Dsx- and Mab3-related transcription factor-1), a conserved transcription factor in different phyla, is a key regulator in sex determination...
  7. Zarkower D. Invertebrates may not be so different after all. Novartis Found Symp. 2002;244:115-26; discussion 126-35, 203-6, 253-7 pubmed
    ..One, Dmrt1, appears to play a conserved role in vertebrate male gonad development...
  8. Yao K, Zhao Y, Zhang T, Cheng H, Zhou R. [Analysis of regulatory regions of mammalian DMRT1 genes]. Yi Chuan. 2006;28:825-30 pubmed
    b>Dmrt1 gene is the first sex differentiation gene found conserved across animal phyla. It plays an important role in mammalian sexual differentiation...
  9. Krentz A, Murphy M, Zhang T, Sarver A, Jain S, Griswold M, et al. Interaction between DMRT1 function and genetic background modulates signaling and pluripotency to control tumor susceptibility in the fetal germ line. Dev Biol. 2013;377:67-78 pubmed publisher
    b>Dmrt1 (doublesex and mab-3 related transcription factor (1) is a regulator of testis development in vertebrates that has been implicated in testicular germ cell tumors of mouse and human...
  10. Hong C, Park B, Saint Jeannet J. The function of Dmrt genes in vertebrate development: it is not just about sex. Dev Biol. 2007;310:1-9 pubmed
    ..Here we review the expression pattern of several members of this family across species and summarize recent findings on the function of a subset of these genes in non-gonadal tissues. ..
  11. Rahmoun M, Lavery R, Laurent Chaballier S, Bellora N, Philip G, Rossitto M, et al. In mammalian foetal testes, SOX9 regulates expression of its target genes by binding to genomic regions with conserved signatures. Nucleic Acids Res. 2017;45:7191-7211 pubmed publisher
    ..by a precise organization of binding motifs for the Sertoli cell reprogramming factors SOX9, GATA4 and DMRT1. As SOX9 biological role in mammalian gonads is to determine Sertoli cells, we correlated this genomic signature ..
  12. Boyer A, Dornan S, Daneau I, Lussier J, Silversides D. Conservation of the function of DMRT1 regulatory sequences in mammalian sex differentiation. Genesis. 2002;34:236-43 pubmed
    Among genes involved in sex determination and differentiation, DMRT1 is the only one characterized to date containing a domain (the DM domain) that is conserved between phyla...
  13. Lovelace D, Gao Z, Mutoji K, Song Y, Ruan J, Hermann B. The regulatory repertoire of PLZF and SALL4 in undifferentiated spermatogonia. Development. 2016;143:1893-906 pubmed publisher
    ..SALL4 also bound gene introns at sites containing motifs for the differentiation factor DMRT1. Moreover, mRNA levels for both unique and shared target genes involved in both SSC self-renewal and ..
  14. Nanda I, Zend Ajusch E, Shan Z, Grutzner F, Schartl M, Burt D, et al. Conserved synteny between the chicken Z sex chromosome and human chromosome 9 includes the male regulatory gene DMRT1: a comparative (re)view on avian sex determination. Cytogenet Cell Genet. 2000;89:67-78 pubmed
    ..Based on chromosome homology maps, we isolated a Z-linked chicken ortholog of DMRT1, which has been implicated in XY sex reversal in humans...
  15. Lindeman R, Gearhart M, Minkina A, Krentz A, Bardwell V, Zarkower D. Sexual cell-fate reprogramming in the ovary by DMRT1. Curr Biol. 2015;25:764-71 pubmed publisher
    ..In mice, Dmrt1 is required for male gonadal differentiation in somatic cells and germ cells [2-4]...
  16. Cui N, Hao G, Zhao Z, Wang F, Cao J, Yang A. MicroRNA-224 regulates self-renewal of mouse spermatogonial stem cells via targeting DMRT1. J Cell Mol Med. 2016;20:1503-12 pubmed publisher
    ..miR-224 promotes differentiation of SSCs via targeting doublesex and Mab-3-related transcription factor 1 (DMRT1). Moreover, WNT/?-catenin signalling pathway is involved in miR-224-mediated regulation of SSCs self-renewal...
  17. Shibata K, Takase M, Nakamura M. The Dmrt1 expression in sex-reversed gonads of amphibians. Gen Comp Endocrinol. 2002;127:232-41 pubmed
    ..Up to date, many genes involved in gonadal differentiation have been isolated in vertebrates. Dmrt1, a gene that contains the DM-domain (Doublesex/Mab-3 DNA-binding motif), is considered to be one of the essential ..
  18. Cooke H, Saunders P. Mouse models of male infertility. Nat Rev Genet. 2002;3:790-801 pubmed
    ..Targeted mutagenesis in the mouse provides a powerful method to analyse these steps and has provided new insights into the origins of male infertility. ..
  19. Nakagawa T, Zhang T, Kushi R, Nakano S, Endo T, Nakagawa M, et al. Regulation of mitosis-meiosis transition by the ubiquitin ligase β-TrCP in male germ cells. Development. 2017;144:4137-4147 pubmed publisher
    ..Specific and timely downregulation of the transcription factor DMRT1, and consequent induction of Stra8 expression, is required for this process in mammals, but the molecular ..
  20. Levasseur A, Paquet M, Boerboom D, Boyer A. Yes-associated protein and WW-containing transcription regulator 1 regulate the expression of sex-determining genes in Sertoli cells, but their inactivation does not cause sex reversal. Biol Reprod. 2017;97:162-175 pubmed publisher
    ..inactivation of Yap and Wwtr1 resulted in a decrease in the mRNA levels of the male sex differentiation genes Dhh, Dmrt1, Sox9, and Wt1, whereas those of genes involved in female differentiation (Wnt4, Rspo1, and Foxl2) were induced...
  21. De Grandi A, Calvari V, Bertini V, Bulfone A, Peverali G, Camerino G, et al. The expression pattern of a mouse doublesex-related gene is consistent with a role in gonadal differentiation. Mech Dev. 2000;90:323-6 pubmed
    ..In humans, a doublesex-related gene (DMRT1) was identified at less than 30 kb from the critical region for sex reversal on chromosome 9p24 (TD9)...
  22. Huang S, Ye L, Chen H. Sex determination and maintenance: the role of DMRT1 and FOXL2. Asian J Androl. 2017;19:619-624 pubmed publisher
    ..These studies have shown that two key genes, doublesex and mad-3 related transcription factor 1 (Dmrt1) and forkhead box L2 (Foxl2), function in a Yin and Yang relationship to maintain the fates of testes or ovaries ..
  23. Ahituv N, Zhu Y, Visel A, Holt A, Afzal V, Pennacchio L, et al. Deletion of ultraconserved elements yields viable mice. PLoS Biol. 2007;5:e234 pubmed
    ..These results, while not inclusive of all the possible phenotypic impact of the deleted sequences, indicate that extreme sequence constraint does not necessarily reflect crucial functions required for viability. ..
  24. Zhou Z, Shirakawa T, Ohbo K, Sada A, Wu Q, Hasegawa K, et al. RNA Binding Protein Nanos2 Organizes Post-transcriptional Buffering System to Retain Primitive State of Mouse Spermatogonial Stem Cells. Dev Cell. 2015;34:96-107 pubmed publisher
    ..This mechanism links mRNA turnover to mTORC1 signaling through Nanos2-containing mRNPs and establishes a post-transcriptional buffering system to facilitate SSC homeostasis in the fluctuating environment within the seminiferous tubule. ..
  25. Ferguson Smith M. The evolution of sex chromosomes and sex determination in vertebrates and the key role of DMRT1. Sex Dev. 2007;1:2-11 pubmed publisher
    ..SRY is the genetic switch in eutherians (placental mammals) and DMRT1 may have that function in birds and at least one species of fish...
  26. Li Y, Zhang L, Hu Y, Han F, Qin Y, Chen M, et al. β-Catenin directs the transformation of testis Sertoli cells to ovarian granulosa-like cells by inducing Foxl2 expression. J Biol Chem. 2017;292:17577-17586 pubmed publisher
    ..Our study provides a new mechanism for Sertoli cell lineage maintenance during gonad development. ..
  27. Georg I, Barrionuevo F, Wiech T, Scherer G. Sox9 and Sox8 are required for basal lamina integrity of testis cords and for suppression of FOXL2 during embryonic testis development in mice. Biol Reprod. 2012;87:99 pubmed publisher
    ..This study shows that Sox9 and Sox8 maintain integrity of the basal lamina to prevent testis cord disintegration and that both factors actively suppress the ovarian program during early testis development. ..
  28. Zarkower D. DMRT genes in vertebrate gametogenesis. Curr Top Dev Biol. 2013;102:327-56 pubmed publisher
    ..b>DMRT1 has the most prominent role and likely regulates testicular differentiation in all vertebrates...
  29. Minkina A, Matson C, Lindeman R, Ghyselinck N, Bardwell V, Zarkower D. DMRT1 protects male gonadal cells from retinoid-dependent sexual transdifferentiation. Dev Cell. 2014;29:511-520 pubmed publisher
    ..can be induced to transdifferentiate to their opposite-sex equivalents by loss of a single transcription factor, DMRT1 in the testis or FOXL2 in the ovary...
  30. Maatouk D, Mork L, Chassot A, Chaboissier M, Capel B. Disruption of mitotic arrest precedes precocious differentiation and transdifferentiation of pregranulosa cells in the perinatal Wnt4 mutant ovary. Dev Biol. 2013;383:295-306 pubmed publisher
    ..This may explain the lack of complete sex reversal in such mutants at the sex-determining stage. ..
  31. Takashima S, Hirose M, Ogonuki N, Ebisuya M, Inoue K, Kanatsu Shinohara M, et al. Regulation of pluripotency in male germline stem cells by Dmrt1. Genes Dev. 2013;27:1949-58 pubmed publisher
    ..This treatment down-regulated Dmrt1, a gene involved in sexual differentiation, meiosis, and pluripotency...
  32. Zhang L, Chen M, Wen Q, Li Y, Wang Y, Wang Y, et al. Reprogramming of Sertoli cells to fetal-like Leydig cells by Wt1 ablation. Proc Natl Acad Sci U S A. 2015;112:4003-8 pubmed publisher
    ..This study thus provides a novel concept for somatic cell fate determination in testis development that may also represent an etiology of male infertility in human patients. ..
  33. Andersson L, Larhammar M, Memic F, Wootz H, Schwochow D, Rubin C, et al. Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice. Nature. 2012;488:642-6 pubmed publisher
    ..The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation...
  34. Chen J, Heckert L. Dmrt1 expression is regulated by follicle-stimulating hormone and phorbol esters in postnatal Sertoli cells. Endocrinology. 2001;142:1167-78 pubmed
    b>Dmrt1 is a recently described gene that is expressed exclusively in the testis and is required for postnatal testis differentiation. Here we describe the expression of Dmrt1 in postnatal rat testis and Sertoli cells...
  35. Zhang T, OATLEY J, Bardwell V, Zarkower D. DMRT1 Is Required for Mouse Spermatogonial Stem Cell Maintenance and Replenishment. PLoS Genet. 2016;12:e1006293 pubmed publisher
    ..Prior work established doublesex- and mab-3-related transcription factor 1 (Dmrt1) as a conserved transcriptional regulator of male sexual differentiation...
  36. Yao K, Lu H, Cheng H, Zhou R. Mutation of siRNA results in thermodynamically unstable duplex which influences knockdown of dmrt1 by RNA interference. Front Biosci. 2006;11:2623-30 pubmed
    ..Furthermore negative effects of the mutation on RNA interference (RNAi) was observed in both mouse dmrt1 transfected COS-7 and Sertoli cells in which endogenous dmrt1 was expressed...
  37. Krentz A, Murphy M, Sarver A, Griswold M, Bardwell V, Zarkower D. DMRT1 promotes oogenesis by transcriptional activation of Stra8 in the mammalian fetal ovary. Dev Biol. 2011;356:63-70 pubmed publisher
    b>Dmrt1 belongs to the DM domain gene family of conserved sexual regulators. In the mouse Dmrt1 is expressed in the genital ridge (the gonadal primordium) in both sexes and then becomes testis-specific shortly after sex determination...
  38. McDermott J, Sanchez G, Chennathukuzhi V, Blanco G. Green fluorescence protein driven by the Na,K-ATPase ?4 isoform promoter is expressed only in male germ cells of mouse testis. J Assist Reprod Genet. 2012;29:1313-25 pubmed publisher
    ..These findings highlight the exquisite spatial and temporal control of expression exerted by the Atp1a4 promoter on Na,K-ATPase ?4, which is particularly well suited to fulfill the special functions of spermatozoa. ..
  39. Barrionuevo F, Hurtado A, Kim G, Real F, Bakkali M, Kopp J, et al. Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration. elife. 2016;5: pubmed publisher
    ..b>Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown...
  40. Hussain S, Tuorto F, Menon S, Blanco S, Cox C, Flores J, et al. The mouse cytosine-5 RNA methyltransferase NSun2 is a component of the chromatoid body and required for testis differentiation. Mol Cell Biol. 2013;33:1561-70 pubmed publisher
    ..Specific NSun2- and Dnmt2-methylated tRNAs decreased in abundance when both methyltransferases were deleted, suggesting that RNA methylation pathways play an essential role in male germ cell differentiation. ..
  41. Lei N, Hornbaker K, Rice D, Karpova T, Agbor V, Heckert L. Sex-specific differences in mouse DMRT1 expression are both cell type- and stage-dependent during gonad development. Biol Reprod. 2007;77:466-75 pubmed
    Immunohistochemistry was used to examine GCNA1, a germ cell-specific protein, together with DMRT1 (Doublesex and Mab-3-related transcription factor-1), a transcription factor implicated in Sertoli cell and germ cell function, in order to ..
  42. Nicol B, Yao H. Gonadal Identity in the Absence of Pro-Testis Factor SOX9 and Pro-Ovary Factor Beta-Catenin in Mice. Biol Reprod. 2015;93:35 pubmed publisher
    ..Our findings not only provide insight into the mechanism of sex determination, but also identify candidate genes that are potentially involved in disorders of sex development. ..