The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform
David Zarkower - One of the best experts on this subject based on the ideXlab platform.
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a sex specific transcription factor controls male identity in a simultaneous hermaphrodite
Nature Communications, 2013Co-Authors: Tracy Chong, John L Brubacher, David Zarkower, James J Collins, Phillip A NewmarkAbstract:Hermaphrodites develop and maintain male and female reproductive organs in a single individual. Chong et al. show that a DM Domain transcription factor is required for male germ cell regeneration and maintains ‘maleness’ in a hermaphrodite, the planarian flatworm Schmidtea mediterranea.
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DMrt genes in vertebrate gametogenesis
Current Topics in Developmental Biology, 2013Co-Authors: David ZarkowerAbstract:Genes containing the DM Domain DNA-binding motif regulate sex determination and sexual differentiation in a broad variety of metazoans, including nematodes, insects, and vertebrates. They can function in primary sex determination or downstream in sexual differentiation, and they can act either throughout the body or in highly restricted cell types. In vertebrates, several DM Domain genes--DMRT genes--play critical roles in gonadal differentiation or gametogenesis. DMRT1 has the most prominent role and likely regulates testicular differentiation in all vertebrates. In the mammalian gonad, DMRT1 exerts both intrinsic and extrinsic control of gametogenesis; it is required for germ cell differentiation in males and regulates meiosis in both sexes, and it is required in supporting cells for the establishment and maintenance of male fate in the testis. These varied functions of DMRT1 serve to coordinate gonadal development and function. In other vertebrates, DMRT1 regulates gonadal differentiation, and it also appears to have played a central role in the evolution of new sex-determining mechanisms in at least three vertebrate clades. This chapter focuses on the regulation of vertebrate gametogenesis by DMRT1.
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sex and the singular DM Domain insights into sexual regulation evolution and plasticity
Nature Reviews Genetics, 2012Co-Authors: Clinton K Matson, David ZarkowerAbstract:Most animals reproduce sexually, but the genetic and molecular mechanisms that determine the eventual sex of each embryo vary remarkably. DM Domain genes, which are related to the insect gene doublesex, are integral to sexual development and its evolution in many metazoans. Recent studies of DM Domain genes reveal mechanisms by which new sexual dimorphisms have evolved in invertebrates and show that one gene, DMrt1, was central to multiple evolutionary transitions between sex-determining mechanisms in vertebrates. In addition, DMrt1 coordinates a surprising array of distinct cell fate decisions in the mammalian gonad and even guards against transdifferentiation of male cells into female cells in the adult testis.
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genome wide analysis of dna binding and transcriptional regulation by the mammalian doublesex homolog DMrt1 in the juvenile testis
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Mark W. Murphy, David Zarkower, Aaron L Sarver, Daren A Rice, Katerina Hatzi, Ari Melnick, Leslie L Heckert, Vivian J. BardwellAbstract:The DM Domain proteins Doublesex- and MAB-3–related transcription factors (DMRTs) are widely conserved in metazoan sex determination and sexual differentiation. One of these proteins, DMRT1, plays diverse and essential roles in development of the vertebrate testis. In mammals DMRT1 is expressed and required in both germ cells and their supporting Sertoli cells. Despite its critical role in testicular development, little is known about how DMRT1 functions as a transcription factor or what genes it binds and regulates. We combined ChIP methods with conditional gene targeting and mRNA expression analysis and identified almost 1,400 promoter-proximal regions bound by DMRT1 in the juvenile mouse testis and determined how expression of the associated mRNAs is affected when DMrt1 is selectively mutated in germ cells or Sertoli cells. These analyses revealed that DMRT1 is a bifunctional transcriptional regulator, activating some genes and repressing others. ChIP analysis using conditional mutant testes showed that DNA binding and transcriptional regulation of individual target genes can differ between germ cells and Sertoli cells. Genes bound by DMRT1 in vivo were enriched for a motif closely resembling the sequence DMRT1 prefers in vitro. Differential response of genes to loss of DMRT1 corresponded to differences in the enriched motif, suggesting that other transacting factors may modulate DMRT1 activity. DMRT1 bound its own promoter and those of six other DMrt genes, indicating auto- and cross-regulation of these genes. Many of the DMRT1 target genes identified here are known to be important for a variety of functions in testicular development; the others are candidates for further investigation.
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cell type autonomous and non autonomous requirements for DMrt1 in postnatal testis differentiation
Developmental Biology, 2007Co-Authors: Shinseog Kim, Vivian J. Bardwell, David ZarkowerAbstract:Genes containing the DM Domain, a conserved DNA binding motif first found in Doublesex of Drosophila and mab-3 of Caenorhabditis elegans, regulate sexual differentiation in multiple phyla. The DM Domain gene DMrt1 is essential for testicular differentiation in vertebrates. In the mouse, DMrt1 is expressed in pre-meiotic germ cells and in Sertoli cells, which provide essential support for spermatogenesis. DMrt1 null mutant mice have severely dysgenic testes in which Sertoli cells and germ cells both fail to differentiate properly after birth. Here we use conditional gene targeting to identify the functions of DMrt1 in each cell type. We find that DMrt1 is required in Sertoli cells for their postnatal differentiation, and for germ line maintenance and for meiotic progression. DMrt1 is required in germ cells for their radial migration to the periphery of the seminiferous tubule where the spermatogenic niche will form, for mitotic reactivation and for survival beyond the first postnatal week. Thus DMrt1 activity is required autonomously in the Sertoli and germ cell lineages, and DMrt1 activity in Sertoli cells is also required non-autonomously to maintain the germ line. These results demonstrate that DMrt1 plays multiple roles in controlling the remodeling and differentiation of the juvenile testis.
Yoshitaka Nagahama - One of the best experts on this subject based on the ideXlab platform.
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rspo1 activated signalling molecules are sufficient to induce ovarian differentiation in xy medaka oryzias latipes
Scientific Reports, 2016Co-Authors: Linyan Zhou, Tapas Charkraborty, Sipra Mohapatra, Yoshitaka Nagahama, Qian Zhou, Yueguang ZhangAbstract:In contrast to our understanding of testicular differentiation, ovarian differentiation is less well understood in vertebrates. In mammals, R-spondin1 (Rspo1), an activator of Wnt/β-catenin signaling pathway, is located upstream of the female sex determination pathway. However, the functions of Rspo1 in ovarian differentiation remain unclear in non-mammalian species. In order to elucidate the detailed functions of Rspo/Wnt signaling pathway in fish sex determination/differentiation, the ectopic expression of the Rspo1 gene was performed in XY medaka (Oryzias latipes). The results obtained demonstrated that the gain of Rspo1 function induced femininity in XY fish. The overexpression of Rspo1 enhanced Wnt4b and β-catenin transcription, and completely suppressed the expression of male-biased genes (DMy, Gsdf, Sox9a2 and DMrt1) as well as testicular differentiation. Gonadal reprograming of Rspo1-over-expressed-XY (Rspo1-OV-XY) fish, induced the production of female-biased genes (Cyp19a1a and Foxl2), estradiol-17β production and further female type secondary sexuality. Moreover, Rspo1-OV-XY females were fertile and produced successive generations. Promoter analyses showed that Rspo1 transcription was directly regulated by DM Domain genes (DMy, the sex-determining gene, and DMrt1) and remained unresponsive to Foxl2. Taken together, our results strongly suggest that Rspo1 is sufficient to activate ovarian development and plays a decisive role in the ovarian differentiation in medaka.
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DMy gene induces male development in genetically female xx medaka fish
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Masaru Matsuda, Mitsuru Sakaizumi, Satoshi Hamaguchi, Tohru Kobayashi, Aya Suzuki, Ai Shinomiya, Masato Kinoshita, Bindhu Paulprasanth, Enlieng Lau, Yoshitaka NagahamaAbstract:Although the sex-determining gene SRY/Sry has been identified in mammals, homologues and genes that have a similar function have yet to be identified in nonmammalian vertebrates. Recently, DMY (the DM-Domain gene on the Y chromosome) was cloned from the sex-determining region on the Y chromosome of the teleost fish medaka (Oryzias latipes). DMY has been shown to be required for the normal development of male individuals. In this study, we show that a 117-kb genomic DNA fragment that carries DMY is able to induce testis differentiation and subsequent male development in XX (genetically female) medaka. In addition, overexpression of DMY cDNA under the control of the CMV promoter also caused XX sex reversal. These results demonstrate that DMY is sufficient for male development in medaka and suggest that the functional difference between the X and Y chromosomes in medaka is a single gene. Our data indicate that DMY is an additional sex-determining gene in vertebrates.
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two DM Domain genes DMy and DMrt1 involved in testicular differentiation and development in the medaka oryzias latipes
Developmental Dynamics, 2004Co-Authors: Tohru Kobayashi, Masaru Matsuda, Hiroko Kajiurakobayashi, Aya Suzuki, Noriko Saito, Masatoshi Nakamoto, Naoki Shibata, Yoshitaka NagahamaAbstract:The recent discovery of the DMY gene (DM Domain gene on Y chromosome and one of the DMRT1 family genes) as a key determinant of male development in the medaka (Oryzias latipes) has led to its designation as the prime candidate gene for sex-determination in this species. This study focused on the sites and pattern of expression of DMY and DMRT1 genes during gonadal differentiation of medaka to further determine their roles in testis development. DMY mRNA and protein are expressed specifically in the somatic cells surrounding primordial germ cells (PGCs) in the early gonadal primordium, before morphological sex differences are seen. However, somatic cells surrounding PGCs never express DMY during the early migratory period. Expression of DMY persists in Sertoli cell lineage cells, from PGC-supporting cells to Sertoli cells, indicating that only DMY-positive cells enclose PGCs during mitotic arrest after hatching. DMRT1 is expressed in spermatogonium-supporting cells after testicular differentiation (20-30 days after hatching), and its expression is much higher than that of DMY in mature testes. In XX sex-reversed testes, DMRT1 is expressed in the Sertoli cell lineage, similar to the expression of DMY in XY testes. These results suggest strongly that DMY regulates PGC proliferation and differentiation sex-specifically during early gonadal differentiation of XY individuals and that DMRT1 regulates spermatogonial differentiation.
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two DM Domain genes DMy and DMrt1 involved in testicular differentiation and development in the medaka oryzias latipes
Developmental Dynamics, 2004Co-Authors: Tohru Kobayashi, Masaru Matsuda, Hiroko Kajiurakobayashi, Aya Suzuki, Noriko Saito, Masatoshi Nakamoto, Naoki Shibata, Yoshitaka NagahamaAbstract:The recent discovery of the DMY gene (DM Domain gene on Y chromosome and one of the DMRT1 family genes) as a key determinant of male development in the medaka (Oryzias latipes) has led to its designation as the prime candidate gene for sex-determination in this species. This study focused on the sites and pattern of expression of DMY and DMRT1 genes during gonadal differentiation of medaka to further determine their roles in testis development. DMY mRNA and protein are expressed specifically in the somatic cells surrounding primordial germ cells (PGCs) in the early gonadal primordium, before morphological sex differences are seen. However, somatic cells surrounding PGCs never express DMY during the early migratory period. Expression of DMY persists in Sertoli cell lineage cells, from PGC-supporting cells to Sertoli cells, indicating that only DMY-positive cells enclose PGCs during mitotic arrest after hatching. DMRT1 is expressed in spermatogonium-supporting cells after testicular differentiation (20–30 days after hatching), and its expression is much higher than that of DMY in mature testes. In XX sex-reversed testes, DMRT1 is expressed in the Sertoli cell lineage, similar to the expression of DMY in XY testes. These results suggest strongly that DMY regulates PGC proliferation and differentiation sex-specifically during early gonadal differentiation of XY individuals and that DMRT1 regulates spermatogonial differentiation. Developmental Dynamics 231:518–526, 2004. © 2004 Wiley-Liss, Inc.
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the sex determining gene of medaka a y specific DM Domain gene DMy is required for male development
Fish Physiology and Biochemistry, 2003Co-Authors: Masaru Matsuda, Yoshitaka Nagahama, Satoshi Hamaguchi, Tohru Kobayashi, Chika Matsuda, Mitsuru SakaizumiAbstract:Although the sex-determining gene Sry has been identified in mammals, no comparable genes have been found in non-mammalian vertebrates. To clone positionally the sex-determining region of the medaka, Oryzias latipes, we generated a Y congenic strain to highlight the genetic differences between the X and Y chromosomes from inbred strains of medaka. We used recombinant breakpoint analysis and deletion analysis of the Y chromosome of a congenic XY female to restrict the sex-determining region to 250-kb stretch of the Y chromosome. Shotgun sequencing of this region predicted 27 genes. Three of these genes were expressed during sexual differentiation. However, only one gene was Y specific. The full-length cDNA sequence of this gene encodes a putative protein of 267 amino acids, including the highly conserved DM Domain. We thus named it DMY. To establish a role for DMY during sexual differentiation, we screened wild medaka populations for naturally occurring DMY mutants. Two XY females with distinct mutations in DMY were found in separate populations. 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. Furthermore, 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 normal testicular development and is a prime candidate for the medaka sex-determining gene.
Vivian J. Bardwell - One of the best experts on this subject based on the ideXlab platform.
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genome wide analysis of dna binding and transcriptional regulation by the mammalian doublesex homolog DMrt1 in the juvenile testis
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Mark W. Murphy, David Zarkower, Aaron L Sarver, Daren A Rice, Katerina Hatzi, Ari Melnick, Leslie L Heckert, Vivian J. BardwellAbstract:The DM Domain proteins Doublesex- and MAB-3–related transcription factors (DMRTs) are widely conserved in metazoan sex determination and sexual differentiation. One of these proteins, DMRT1, plays diverse and essential roles in development of the vertebrate testis. In mammals DMRT1 is expressed and required in both germ cells and their supporting Sertoli cells. Despite its critical role in testicular development, little is known about how DMRT1 functions as a transcription factor or what genes it binds and regulates. We combined ChIP methods with conditional gene targeting and mRNA expression analysis and identified almost 1,400 promoter-proximal regions bound by DMRT1 in the juvenile mouse testis and determined how expression of the associated mRNAs is affected when DMrt1 is selectively mutated in germ cells or Sertoli cells. These analyses revealed that DMRT1 is a bifunctional transcriptional regulator, activating some genes and repressing others. ChIP analysis using conditional mutant testes showed that DNA binding and transcriptional regulation of individual target genes can differ between germ cells and Sertoli cells. Genes bound by DMRT1 in vivo were enriched for a motif closely resembling the sequence DMRT1 prefers in vitro. Differential response of genes to loss of DMRT1 corresponded to differences in the enriched motif, suggesting that other transacting factors may modulate DMRT1 activity. DMRT1 bound its own promoter and those of six other DMrt genes, indicating auto- and cross-regulation of these genes. Many of the DMRT1 target genes identified here are known to be important for a variety of functions in testicular development; the others are candidates for further investigation.
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cell type autonomous and non autonomous requirements for DMrt1 in postnatal testis differentiation
Developmental Biology, 2007Co-Authors: Shinseog Kim, Vivian J. Bardwell, David ZarkowerAbstract:Genes containing the DM Domain, a conserved DNA binding motif first found in Doublesex of Drosophila and mab-3 of Caenorhabditis elegans, regulate sexual differentiation in multiple phyla. The DM Domain gene DMrt1 is essential for testicular differentiation in vertebrates. In the mouse, DMrt1 is expressed in pre-meiotic germ cells and in Sertoli cells, which provide essential support for spermatogenesis. DMrt1 null mutant mice have severely dysgenic testes in which Sertoli cells and germ cells both fail to differentiate properly after birth. Here we use conditional gene targeting to identify the functions of DMrt1 in each cell type. We find that DMrt1 is required in Sertoli cells for their postnatal differentiation, and for germ line maintenance and for meiotic progression. DMrt1 is required in germ cells for their radial migration to the periphery of the seminiferous tubule where the spermatogenic niche will form, for mitotic reactivation and for survival beyond the first postnatal week. Thus DMrt1 activity is required autonomously in the Sertoli and germ cell lineages, and DMrt1 activity in Sertoli cells is also required non-autonomously to maintain the germ line. These results demonstrate that DMrt1 plays multiple roles in controlling the remodeling and differentiation of the juvenile testis.
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vertebrate DM Domain proteins bind similar dna sequences and can heterodimerize on dna
BMC Molecular Biology, 2007Co-Authors: Mark W. Murphy, David Zarkower, Vivian J. BardwellAbstract:The DM Domain is a zinc finger-like DNA binding motif first identified in the sexual regulatory proteins Doublesex (DSX) and MAB-3, and is widely conserved among metazoans. DM Domain proteins regulate sexual differentiation in at least three phyla and also control other aspects of development, including vertebrate segmentation. Most DM Domain proteins share little similarity outside the DM Domain. DSX and MAB-3 bind partially overlapping DNA sequences, and DSX has been shown to interact with DNA via the minor groove without inducing DNA bending. DSX and MAB-3 exhibit unusually high DNA sequence specificity relative to other minor groove binding proteins. 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. We used a random oligonucleotide in vitro selection method to determine DNA binding sites for six of the seven proteins. These proteins selected sites resembling that of DSX despite differences in the sequence of the DM Domain recognition helix, but they varied in binding efficiency and in preferences for particular nucleotides, and some behaved anomalously in gel mobility shift assays. DMRT1 protein from mouse testis extracts binds the sequence we determined, and the DMRT proteins can bind their in vitro-defined sites in transfected cells. We also find that some DMRT proteins can bind DNA as heterodimers. Our results suggest that target gene specificity of the DMRT proteins does not derive exclusively from major differences in DNA binding specificity. Instead target specificity may come from more subtle differences in DNA binding preference between different homodimers, together with differences in binding specificity between homodimers versus heterodimers.
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mice mutant in the DM Domain gene DMrt4 are viable and fertile but have polyovular follicles
Molecular and Cellular Biology, 2006Co-Authors: Jorune Balciuniene, Vivian J. Bardwell, David ZarkowerAbstract:Proteins containing the DM Domain, a zinc finger-like DNA binding motif, have been implicated in sexual differentiation in diverse metazoan organisms. Of seven mammalian DM Domain genes, only DMrt1 and DMrt2 have been functionally analyzed. Here, we report expression analysis and targeted disruption of DMrt4 (also called DMrtA1) in the mouse. DMrt4 is widely expressed during embryonic and postnatal development. However, we find that mice homozygous for a putative null mutation in DMrt4 develop essentially normally, undergo full sexual differentiation in both sexes, and are fertile. We observed two potential mutant phenotypes in DMrt4 mutant mice. First, ovaries of most mutant females have polyovular follicles, suggesting a role in folliculogenesis. Second, 25% of mutant males consistently exhibited copulatory behavior toward other males. We also tested potential redundancy between DMrt4 and two other gonadally expressed DM Domain genes, DMrt1 and DMrt7. We observed no enhancement of gonadal phenotypes in the double mutants, suggesting that these genes function independently in gonadal development.
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A DM Domain protein from a coral, Acropora millepora, homologous to proteins important for sex determination
Evolution and Development, 2003Co-Authors: Steven W. Miller, David C Hayward, David Zarkower, David J. Miller, Vivian J. Bardwell, Eldon E. Ball, Thomas A. Bunch, Danny L. BrowerAbstract:The identification and functional studies of DM Domain-containing proteins Doublesex, MAB-3, and DMRT1 indicated that flies, nematodes, and humans share at least some of the molecular mechanisms of sex determination. We identified a gene, AmDM1, from the coral Acropora millepora that encodes a homologous DM Domain-containing protein. Molecular analyses show that the AmDM1 primary transcript is processed to generate four different messenger RNAs. Alternative use of two polyadenylation sites produces transcripts that vary only in the 3' untranslated regions, whereas alternative splicing generates transcripts with and without the region coding for the DM Domain. All the transcripts include a second motif, the DMA Domain, which is found in a number of other proteins containing a DM Domain. Hermaphroditic A. millepora differentiates sexual cells seasonally before the spring spawn, and Northern blot analysis shows that the AmDM1 transcripts are present at higher levels during sexual differentiation. The non-DM Domain-containing messages are also present at significant levels in late embryos, but DM Domain transcripts are extremely rare at this stage. These data suggest that the association of DM Domain proteins and sexual determination or differentiation predates the separation of the Cnidaria from the rest of the Metazoa.
Masaru Matsuda - One of the best experts on this subject based on the ideXlab platform.
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DMy gene induces male development in genetically female xx medaka fish
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Masaru Matsuda, Mitsuru Sakaizumi, Satoshi Hamaguchi, Tohru Kobayashi, Aya Suzuki, Ai Shinomiya, Masato Kinoshita, Bindhu Paulprasanth, Enlieng Lau, Yoshitaka NagahamaAbstract:Although the sex-determining gene SRY/Sry has been identified in mammals, homologues and genes that have a similar function have yet to be identified in nonmammalian vertebrates. Recently, DMY (the DM-Domain gene on the Y chromosome) was cloned from the sex-determining region on the Y chromosome of the teleost fish medaka (Oryzias latipes). DMY has been shown to be required for the normal development of male individuals. In this study, we show that a 117-kb genomic DNA fragment that carries DMY is able to induce testis differentiation and subsequent male development in XX (genetically female) medaka. In addition, overexpression of DMY cDNA under the control of the CMV promoter also caused XX sex reversal. These results demonstrate that DMY is sufficient for male development in medaka and suggest that the functional difference between the X and Y chromosomes in medaka is a single gene. Our data indicate that DMY is an additional sex-determining gene in vertebrates.
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two DM Domain genes DMy and DMrt1 involved in testicular differentiation and development in the medaka oryzias latipes
Developmental Dynamics, 2004Co-Authors: Tohru Kobayashi, Masaru Matsuda, Hiroko Kajiurakobayashi, Aya Suzuki, Noriko Saito, Masatoshi Nakamoto, Naoki Shibata, Yoshitaka NagahamaAbstract:The recent discovery of the DMY gene (DM Domain gene on Y chromosome and one of the DMRT1 family genes) as a key determinant of male development in the medaka (Oryzias latipes) has led to its designation as the prime candidate gene for sex-determination in this species. This study focused on the sites and pattern of expression of DMY and DMRT1 genes during gonadal differentiation of medaka to further determine their roles in testis development. DMY mRNA and protein are expressed specifically in the somatic cells surrounding primordial germ cells (PGCs) in the early gonadal primordium, before morphological sex differences are seen. However, somatic cells surrounding PGCs never express DMY during the early migratory period. Expression of DMY persists in Sertoli cell lineage cells, from PGC-supporting cells to Sertoli cells, indicating that only DMY-positive cells enclose PGCs during mitotic arrest after hatching. DMRT1 is expressed in spermatogonium-supporting cells after testicular differentiation (20-30 days after hatching), and its expression is much higher than that of DMY in mature testes. In XX sex-reversed testes, DMRT1 is expressed in the Sertoli cell lineage, similar to the expression of DMY in XY testes. These results suggest strongly that DMY regulates PGC proliferation and differentiation sex-specifically during early gonadal differentiation of XY individuals and that DMRT1 regulates spermatogonial differentiation.
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two DM Domain genes DMy and DMrt1 involved in testicular differentiation and development in the medaka oryzias latipes
Developmental Dynamics, 2004Co-Authors: Tohru Kobayashi, Masaru Matsuda, Hiroko Kajiurakobayashi, Aya Suzuki, Noriko Saito, Masatoshi Nakamoto, Naoki Shibata, Yoshitaka NagahamaAbstract:The recent discovery of the DMY gene (DM Domain gene on Y chromosome and one of the DMRT1 family genes) as a key determinant of male development in the medaka (Oryzias latipes) has led to its designation as the prime candidate gene for sex-determination in this species. This study focused on the sites and pattern of expression of DMY and DMRT1 genes during gonadal differentiation of medaka to further determine their roles in testis development. DMY mRNA and protein are expressed specifically in the somatic cells surrounding primordial germ cells (PGCs) in the early gonadal primordium, before morphological sex differences are seen. However, somatic cells surrounding PGCs never express DMY during the early migratory period. Expression of DMY persists in Sertoli cell lineage cells, from PGC-supporting cells to Sertoli cells, indicating that only DMY-positive cells enclose PGCs during mitotic arrest after hatching. DMRT1 is expressed in spermatogonium-supporting cells after testicular differentiation (20–30 days after hatching), and its expression is much higher than that of DMY in mature testes. In XX sex-reversed testes, DMRT1 is expressed in the Sertoli cell lineage, similar to the expression of DMY in XY testes. These results suggest strongly that DMY regulates PGC proliferation and differentiation sex-specifically during early gonadal differentiation of XY individuals and that DMRT1 regulates spermatogonial differentiation. Developmental Dynamics 231:518–526, 2004. © 2004 Wiley-Liss, Inc.
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the sex determining gene of medaka a y specific DM Domain gene DMy is required for male development
Fish Physiology and Biochemistry, 2003Co-Authors: Masaru Matsuda, Yoshitaka Nagahama, Satoshi Hamaguchi, Tohru Kobayashi, Chika Matsuda, Mitsuru SakaizumiAbstract:Although the sex-determining gene Sry has been identified in mammals, no comparable genes have been found in non-mammalian vertebrates. To clone positionally the sex-determining region of the medaka, Oryzias latipes, we generated a Y congenic strain to highlight the genetic differences between the X and Y chromosomes from inbred strains of medaka. We used recombinant breakpoint analysis and deletion analysis of the Y chromosome of a congenic XY female to restrict the sex-determining region to 250-kb stretch of the Y chromosome. Shotgun sequencing of this region predicted 27 genes. Three of these genes were expressed during sexual differentiation. However, only one gene was Y specific. The full-length cDNA sequence of this gene encodes a putative protein of 267 amino acids, including the highly conserved DM Domain. We thus named it DMY. To establish a role for DMY during sexual differentiation, we screened wild medaka populations for naturally occurring DMY mutants. Two XY females with distinct mutations in DMY were found in separate populations. 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. Furthermore, 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 normal testicular development and is a prime candidate for the medaka sex-determining gene.
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oryzias curvinotus has DMy a gene that is required for male development in the medaka o latipes
Zoological Science, 2003Co-Authors: Masaru Matsuda, Yota Toyazaki, Yoshitaka Nagahama, Tadashi Sato, Satoshi Hamaguchi, Mitsuru SakaizumiAbstract:DMY is a Y-specific DM-Domain gene required for male development and appears to be the sex-determining gene in the teleost fish medaka, Oryzias latipes. Although the genomic region containing DMY appears to have originated through duplication of the DMRT1 region, it is unknown when the duplication occurred. Here we show that O. curvinotus also has the DMY gene on the Y chromosome, which is homologous to the Y chromosome of medaka, and that DMY is expressed in XY embryos. A phylogenetic tree based on the amino acid sequence including the DM-Domain shows that DMY was derived from DMRT1 immediately before speciation of O. latipes and O. curvinotus.
Tohru Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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DMy gene induces male development in genetically female xx medaka fish
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Masaru Matsuda, Mitsuru Sakaizumi, Satoshi Hamaguchi, Tohru Kobayashi, Aya Suzuki, Ai Shinomiya, Masato Kinoshita, Bindhu Paulprasanth, Enlieng Lau, Yoshitaka NagahamaAbstract:Although the sex-determining gene SRY/Sry has been identified in mammals, homologues and genes that have a similar function have yet to be identified in nonmammalian vertebrates. Recently, DMY (the DM-Domain gene on the Y chromosome) was cloned from the sex-determining region on the Y chromosome of the teleost fish medaka (Oryzias latipes). DMY has been shown to be required for the normal development of male individuals. In this study, we show that a 117-kb genomic DNA fragment that carries DMY is able to induce testis differentiation and subsequent male development in XX (genetically female) medaka. In addition, overexpression of DMY cDNA under the control of the CMV promoter also caused XX sex reversal. These results demonstrate that DMY is sufficient for male development in medaka and suggest that the functional difference between the X and Y chromosomes in medaka is a single gene. Our data indicate that DMY is an additional sex-determining gene in vertebrates.
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two DM Domain genes DMy and DMrt1 involved in testicular differentiation and development in the medaka oryzias latipes
Developmental Dynamics, 2004Co-Authors: Tohru Kobayashi, Masaru Matsuda, Hiroko Kajiurakobayashi, Aya Suzuki, Noriko Saito, Masatoshi Nakamoto, Naoki Shibata, Yoshitaka NagahamaAbstract:The recent discovery of the DMY gene (DM Domain gene on Y chromosome and one of the DMRT1 family genes) as a key determinant of male development in the medaka (Oryzias latipes) has led to its designation as the prime candidate gene for sex-determination in this species. This study focused on the sites and pattern of expression of DMY and DMRT1 genes during gonadal differentiation of medaka to further determine their roles in testis development. DMY mRNA and protein are expressed specifically in the somatic cells surrounding primordial germ cells (PGCs) in the early gonadal primordium, before morphological sex differences are seen. However, somatic cells surrounding PGCs never express DMY during the early migratory period. Expression of DMY persists in Sertoli cell lineage cells, from PGC-supporting cells to Sertoli cells, indicating that only DMY-positive cells enclose PGCs during mitotic arrest after hatching. DMRT1 is expressed in spermatogonium-supporting cells after testicular differentiation (20-30 days after hatching), and its expression is much higher than that of DMY in mature testes. In XX sex-reversed testes, DMRT1 is expressed in the Sertoli cell lineage, similar to the expression of DMY in XY testes. These results suggest strongly that DMY regulates PGC proliferation and differentiation sex-specifically during early gonadal differentiation of XY individuals and that DMRT1 regulates spermatogonial differentiation.
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two DM Domain genes DMy and DMrt1 involved in testicular differentiation and development in the medaka oryzias latipes
Developmental Dynamics, 2004Co-Authors: Tohru Kobayashi, Masaru Matsuda, Hiroko Kajiurakobayashi, Aya Suzuki, Noriko Saito, Masatoshi Nakamoto, Naoki Shibata, Yoshitaka NagahamaAbstract:The recent discovery of the DMY gene (DM Domain gene on Y chromosome and one of the DMRT1 family genes) as a key determinant of male development in the medaka (Oryzias latipes) has led to its designation as the prime candidate gene for sex-determination in this species. This study focused on the sites and pattern of expression of DMY and DMRT1 genes during gonadal differentiation of medaka to further determine their roles in testis development. DMY mRNA and protein are expressed specifically in the somatic cells surrounding primordial germ cells (PGCs) in the early gonadal primordium, before morphological sex differences are seen. However, somatic cells surrounding PGCs never express DMY during the early migratory period. Expression of DMY persists in Sertoli cell lineage cells, from PGC-supporting cells to Sertoli cells, indicating that only DMY-positive cells enclose PGCs during mitotic arrest after hatching. DMRT1 is expressed in spermatogonium-supporting cells after testicular differentiation (20–30 days after hatching), and its expression is much higher than that of DMY in mature testes. In XX sex-reversed testes, DMRT1 is expressed in the Sertoli cell lineage, similar to the expression of DMY in XY testes. These results suggest strongly that DMY regulates PGC proliferation and differentiation sex-specifically during early gonadal differentiation of XY individuals and that DMRT1 regulates spermatogonial differentiation. Developmental Dynamics 231:518–526, 2004. © 2004 Wiley-Liss, Inc.
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the sex determining gene of medaka a y specific DM Domain gene DMy is required for male development
Fish Physiology and Biochemistry, 2003Co-Authors: Masaru Matsuda, Yoshitaka Nagahama, Satoshi Hamaguchi, Tohru Kobayashi, Chika Matsuda, Mitsuru SakaizumiAbstract:Although the sex-determining gene Sry has been identified in mammals, no comparable genes have been found in non-mammalian vertebrates. To clone positionally the sex-determining region of the medaka, Oryzias latipes, we generated a Y congenic strain to highlight the genetic differences between the X and Y chromosomes from inbred strains of medaka. We used recombinant breakpoint analysis and deletion analysis of the Y chromosome of a congenic XY female to restrict the sex-determining region to 250-kb stretch of the Y chromosome. Shotgun sequencing of this region predicted 27 genes. Three of these genes were expressed during sexual differentiation. However, only one gene was Y specific. The full-length cDNA sequence of this gene encodes a putative protein of 267 amino acids, including the highly conserved DM Domain. We thus named it DMY. To establish a role for DMY during sexual differentiation, we screened wild medaka populations for naturally occurring DMY mutants. Two XY females with distinct mutations in DMY were found in separate populations. 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. Furthermore, 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 normal testicular development and is a prime candidate for the medaka sex-determining gene.
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DMy is a y specific DM Domain gene required for male development in the medaka fish
Nature, 2002Co-Authors: Masaru Matsuda, Yoshitaka Nagahama, Tadashi Sato, Tohru Kobayashi, Naoki Shibata, Chika Matsuda, Ai Shinomiya, Craig E Morrey, Shuichi Asakawa, Nobuyoshi ShimizuAbstract:Although the sex-determining gene Sry has been identified in mammals1, 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-related2 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.