title: The zinc-finger protein basonuclin 2 is required for proper mitotic arrest, prevention of premature meiotic initiation and meiotic progression in mouse male germ cells.
abstract: Absence of mitosis and meiosis are distinguishing properties of male germ cells during late fetal and early neonatal periods. Repressors of male germ cell meiosis have been identified, but mitotic repressors are largely unknown, and no protein repressing both meiosis and mitosis is known. We demonstrate here that the zinc-finger protein BNC2 is present in male but not in female germ cells. In testis, BNC2 exists as several spliced isoforms and presumably binds to DNA. Within the male germ cell lineage, BNC2 is restricted to prospermatogonia and undifferentiated spermatogonia. Fetal prospermatogonia that lack BNC2 multiply excessively on embryonic day (E)14.5 and reenter the cell cycle prematurely. Mutant prospermatogonia also engage in abnormal meiosis; on E17.5, Bnc2(-/-) prospermatogonia start synthesizing the synaptonemal protein SYCP3, and by the time of birth, many Bnc2(-/-) prospermatogonia have accumulated large amounts of nonfilamentous SYCP3, thus appearing to be blocked at leptonema. Bnc2(-/-) prospermatogonia do not undergo proper male differentiation, as they lack almost all the mRNA for the male-specific methylation protein DNMT3L and have increased levels of mRNAs that encode meiotic proteins, including STRA8. Bnc2(-/-) prospermatogonia can produce spermatogonia, but these enter meiosis prematurely and undergo massive apoptotic death during meiotic prophase. This study identifies BNC2 as a major regulator of male germ stem cells, which is required for repression of meiosis and mitosis in prospermatogonia, and for meiosis progression during spermatogenesis. In view of the extreme evolutionary conservation of BNC2, the findings described here are likely to apply to many species.
authors.affiliation: Laboratoire de physiologie cérébrale, Centre National de la Recherche Scientifique, Université Paris Descartes, UMR 8118, Paris, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Vanhoutteghem
authors.affiliation: Laboratoire de développement des gonades, Université Paris Diderot, Sorbonne Paris Cité, INSERM U967, CEA/DSV/iRCM/SCSR, Fontenay-aux-Roses F-92265, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Messiaen
authors.affiliation: Laboratoire de physiologie cérébrale, Centre National de la Recherche Scientifique, Université Paris Descartes, UMR 8118, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Hervé
authors.affiliation: Laboratoire de physiologie cérébrale, Centre National de la Recherche Scientifique, Université Paris Descartes, UMR 8118, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Delhomme
authors.affiliation: Laboratoire de développement des gonades, Université Paris Diderot, Sorbonne Paris Cité, INSERM U967, CEA/DSV/iRCM/SCSR, Fontenay-aux-Roses F-92265, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Moison
authors.affiliation: Service central de microscopie, Centre Universitaire des Saints-Pères, Université Paris Descartes, Paris, France.
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Petit
authors.affiliation: Laboratoire de développement des gonades, Université Paris Diderot, Sorbonne Paris Cité, INSERM U967, CEA/DSV/iRCM/SCSR, Fontenay-aux-Roses F-92265, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Rouiller-Fabre
authors.affiliation: Laboratoire de développement des gonades, Université Paris Diderot, Sorbonne Paris Cité, INSERM U967, CEA/DSV/iRCM/SCSR, Fontenay-aux-Roses F-92265, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Livera
authors.affiliation: Laboratoire de physiologie cérébrale, Centre National de la Recherche Scientifique, Université Paris Descartes, UMR 8118, Paris, France philippe.djian@parisdescartes.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Djian
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D007150:Immunohistochemistry; D008297:Male; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013093:Spermatogonia / Q000378:metabolism / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C490062:Sycp3 protein, mouse; C484528:basonuclin 2, mouse; C498796:Dnmt3l protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: BNC2; Gonocytes; Mouse; Spermatogonia; Transcription