title: Germ cell nuclear factor regulates gametogenesis in developing gonads.
abstract: Expression of germ cell nuclear factor (GCNF; Nr6a1), an orphan member of the nuclear receptor gene family of transcription factors, during gastrulation and neurulation is critical for normal embryogenesis in mice. Gcnf represses the expression of the POU-domain transcription factor Oct4 (Pou5f1) during mouse post-implantation development. Although Gcnf expression is not critical for the embryonic segregation of the germ cell lineage, we found that sexually dimorphic expression of Gcnf in germ cells correlates with the expression of pluripotency-associated genes, such as Oct4, Sox2, and Nanog, as well as the early meiotic marker gene Stra8. To elucidate the role of Gcnf during mouse germ cell differentiation, we generated an ex vivo Gcnf-knockdown model in combination with a regulated CreLox mutation of Gcnf. Lack of Gcnf impairs normal spermatogenesis and oogenesis in vivo, as well as the derivation of germ cells from embryonic stem cells (ESCs) in vitro. Inactivation of the Gcnf gene in vivo leads to loss of repression of Oct4 expression in both male and female gonads.
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Davood
authors.initials: D
authors.lastname: Sabour
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Xueping
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America; Centre for Inflammatory Diseases and Molecular Therapies, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Arthur C K
authors.initials: AC
authors.lastname: Chung
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America; INSERM, U693, Faculté de Médecine Paris-Sud, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Le Menuet
authors.affiliation: Center for Stem Cell Research, Institute of Biomedical Sciences and Technology, Konkuk University, Seoul, Republic of Korea; Department of Neuroscience, School of Medicine, Institute of Biomedical Sciences and Technology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Kinarm
authors.initials: K
authors.lastname: Ko
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Tapia
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany; Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastián, Spain.
authors.forename: Marcos J
authors.initials: MJ
authors.lastname: Araúzo-Bravo
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Luca
authors.initials: L
authors.lastname: Gentile
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Greber
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Hübner
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Palo Alto, California, United States of America.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Sebastiano
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Guangming
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany; Medical Faculty, University of Münster, Münster, Germany.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Schöler
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Austin J
authors.initials: AJ
authors.lastname: Cooney
mesh_terms: D000818:Animals; D005260:Female; D005718:Gametogenesis / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D057136:Nuclear Receptor Subfamily 6, Group A, Member 1 / Q000235:genetics / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism
chemical_list: D057136:Nuclear Receptor Subfamily 6, Group A, Member 1; D050814:Octamer Transcription Factor-3