IHB OpenIR  > 鱼类生物学及渔业生物技术研究中心  > 期刊论文
Zebrafish dmrta2 Regulates the Expression of cdkn2c in Spermatogenesis in the Adult Testis
Xu, Shan1; Xia, Wei2; Zohar, Yonathan2; Gui, Jian-Fang1; Gui, JF (reprint author), Chinese Acad Sci, Grad Sch, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan, Peoples R China.
2013
Source PublicationBIOLOGY OF REPRODUCTION
ISSN0006-3363
Volume88Issue:1
AbstractThe exact function of the doublesex and mab-3 related transcription factor-like family a2 gene (dmrta2) has remained largely unknown possibly because of its functional redundancy with dmrta1 in most vertebrates. In this study, dmrta1 was demonstrated to likely be absent in the zebrafish genome, which facilitated our functional analysis of dmrta2 in this model organism. To analyze its gene function in embryos and adults, we generated a mutant form of Dmrta2 (R106Q, Dmrta2(RQ)) with its in vitro DNA-binding capacity abolished and a transgenic line for the inducible expression of this mutant Dmrta2(RQ) upon doxycycline (Dox) treatment. Preferential dmrta2 expression was detected in the developing brain during embryogenesis and in the adult testis. During embryogenesis, Dmrta2(RQ) expression caused severe embryonic development defects and dramatic expression changes of two telencephalic marker genes, fibroblast growth factor 8a (fgf8a), and empty spiracles homolog 1 (emx1). In adults, the inducible Dmrta2(RQ) expression occurred specifically in the adult testis and recapitulated the endogenous dmrta2 expression in this organ. Intriguingly, adult males expressing dmrta2(RQ) showed normal spermatogenesis and were fertile, but the expression of cyclin-dependent kinase inhibitor 2C (cdkn2c), which is evolutionarily clustered with dmrta2, was significantly suppressed during spermatogenesis. Further protein-binding and promoter mutation analysis indicated that a putative Dmrta2-binding site on the cdkn2c promoter was required for sustaining the normal expression of cdkn2c during zebrafish spermatogenesis, suggesting that Dmrta2 might regulate the expression of cdkn2c.; The exact function of the doublesex and mab-3 related transcription factor-like family a2 gene (dmrta2) has remained largely unknown possibly because of its functional redundancy with dmrta1 in most vertebrates. In this study, dmrta1 was demonstrated to likely be absent in the zebrafish genome, which facilitated our functional analysis of dmrta2 in this model organism. To analyze its gene function in embryos and adults, we generated a mutant form of Dmrta2 (R106Q, Dmrta2(RQ)) with its in vitro DNA-binding capacity abolished and a transgenic line for the inducible expression of this mutant Dmrta2(RQ) upon doxycycline (Dox) treatment. Preferential dmrta2 expression was detected in the developing brain during embryogenesis and in the adult testis. During embryogenesis, Dmrta2(RQ) expression caused severe embryonic development defects and dramatic expression changes of two telencephalic marker genes, fibroblast growth factor 8a (fgf8a), and empty spiracles homolog 1 (emx1). In adults, the inducible Dmrta2(RQ) expression occurred specifically in the adult testis and recapitulated the endogenous dmrta2 expression in this organ. Intriguingly, adult males expressing dmrta2(RQ) showed normal spermatogenesis and were fertile, but the expression of cyclin-dependent kinase inhibitor 2C (cdkn2c), which is evolutionarily clustered with dmrta2, was significantly suppressed during spermatogenesis. Further protein-binding and promoter mutation analysis indicated that a putative Dmrta2-binding site on the cdkn2c promoter was required for sustaining the normal expression of cdkn2c during zebrafish spermatogenesis, suggesting that Dmrta2 might regulate the expression of cdkn2c.
SubtypeArticle
KeywordEmbryo Fish Reproduction Gametogenesis Gene Regulation Genomics
Department[Xu, Shan ; Gui, Jian-Fang] Chinese Acad Sci, Grad Sch, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan, Peoples R China ; [Xia, Wei ; Zohar, Yonathan] Univ Maryland Baltimore Cty, Dept Marine Biotechnol, Baltimore, MD 21228 USA
DOI10.1095/biolreprod.112.105130
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNational Key Basic Research Program of China [2010CB126301]; Special Fund for Agro-scientific Research in the Public Interest [200903046]; Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ17] ; National Key Basic Research Program of China [2010CB126301]; Special Fund for Agro-scientific Research in the Public Interest [200903046]; Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ17] ; National Key Basic Research Program of China [2010CB126301]; Special Fund for Agro-scientific Research in the Public Interest [200903046]; Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ17] ; National Key Basic Research Program of China [2010CB126301]; Special Fund for Agro-scientific Research in the Public Interest [200903046]; Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ17]
Indexed BySCI
Language英语
WOS Research AreaReproductive Biology
WOS SubjectReproductive Biology
WOS IDWOS:000314357700013
WOS KeywordDM-DOMAIN GENE ; DEPENDENT KINASE INHIBITORS ; SEX DETERMINATION ; RESTRICTED EXPRESSION ; EVOLUTIONARY DYNAMICS ; XENOPUS-LAEVIS ; MEDAKA FISH ; DNA-BINDING ; DOUBLESEX ; MOUSE
Funding OrganizationNational Key Basic Research Program of China [2010CB126301]; Special Fund for Agro-scientific Research in the Public Interest [200903046]; Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ17] ; National Key Basic Research Program of China [2010CB126301]; Special Fund for Agro-scientific Research in the Public Interest [200903046]; Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ17] ; National Key Basic Research Program of China [2010CB126301]; Special Fund for Agro-scientific Research in the Public Interest [200903046]; Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ17] ; National Key Basic Research Program of China [2010CB126301]; Special Fund for Agro-scientific Research in the Public Interest [200903046]; Autonomous Project of the State Key Laboratory of Freshwater Ecology and Biotechnology [2011FBZ17]
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Cited Times:13[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/19310
Collection鱼类生物学及渔业生物技术研究中心_期刊论文
Corresponding AuthorGui, JF (reprint author), Chinese Acad Sci, Grad Sch, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan, Peoples R China.
Affiliation1.Chinese Acad Sci, Grad Sch, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan, Peoples R China
2.Univ Maryland Baltimore Cty, Dept Marine Biotechnol, Baltimore, MD 21228 USA
Recommended Citation
GB/T 7714
Xu, Shan,Xia, Wei,Zohar, Yonathan,et al. Zebrafish dmrta2 Regulates the Expression of cdkn2c in Spermatogenesis in the Adult Testis[J]. BIOLOGY OF REPRODUCTION,2013,88(1).
APA Xu, Shan,Xia, Wei,Zohar, Yonathan,Gui, Jian-Fang,&Gui, JF .(2013).Zebrafish dmrta2 Regulates the Expression of cdkn2c in Spermatogenesis in the Adult Testis.BIOLOGY OF REPRODUCTION,88(1).
MLA Xu, Shan,et al."Zebrafish dmrta2 Regulates the Expression of cdkn2c in Spermatogenesis in the Adult Testis".BIOLOGY OF REPRODUCTION 88.1(2013).
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