title: SOX4 regulates gonad morphogenesis and promotes male germ cell differentiation in mice.
abstract: The group C SOX transcription factors SOX4, -11 and -12 play important and mutually overlapping roles in development of a number of organs. Here, we examined the role of SoxC genes during gonadal development in mice. All three genes were expressed in developing gonads of both sexes, predominantly in somatic cells, with Sox4 being most strongly expressed. Sox4 deficiency resulted in elongation of both ovaries and testes, and an increased number of testis cords. While female germ cells entered meiosis normally, male germ cells showed reduced levels of differentiation markers Nanos2 and Dnmt3l and increased levels of pluripotency genes Cripto and Nanog, suggesting that SOX4 may normally act to restrict the pluripotency period of male germ cells and ensure their proper differentiation. Finally, our data reveal that SOX4 (and, to a lesser extent, SOX11 and -12) repressed transcription of the sex-determining gene Sox9 via an upstream testis-specific enhancer core (TESCO) element in fetal gonads, raising the possibility that SOXC proteins may function as transcriptional repressors in a context-dependent manner.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island,550 University Avenue, Charlottetown, PE, Canada C1A 4P3.
authors.forename: Michel
authors.initials: M
authors.lastname: Arsenault
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Ee Ting
authors.initials: ET
authors.lastname: Ng
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Enya
authors.initials: E
authors.lastname: Longmuss
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Tevin Chui-Ying
authors.initials: TC
authors.lastname: Chau
authors.affiliation: Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island,550 University Avenue, Charlottetown, PE, Canada C1A 4P3.
authors.forename: Sunny
authors.initials: S
authors.lastname: Hartwig
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: p.koopman@imb.uq.edu.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Koopman
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D005260:Female; D005333:Fetus / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009024:Morphogenesis; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051876:Sex-Determining Region Y Protein / Q000378:metabolism; D013091:Spermatogenesis; D013737:Testis / Q000166:cytology / Q000254:growth & development*
chemical_list: D055751:SOXC Transcription Factors; D051876:Sex-Determining Region Y Protein; C489990:Sox4 protein, mouse; C497746:Sry protein, mouse
keywords: Gonad development; Ovary; Sex determination; Sox9; SoxC; Testis