title: Retinoid signaling controls spermatogonial differentiation by regulating expression of replication-dependent core histone genes.
abstract: Retinoic acid (RA) signaling is crucial for spermatogonial differentiation, which is a key step for spermatogenesis. We explored the mechanisms underlying spermatogonial differentiation by targeting expression of a dominant-negative mutant of retinoic acid receptor α (RARα) specifically to the germ cells of transgenic mice to subvert the activity of endogenous receptors. Here we show that: (1) inhibition of retinoid signaling in germ cells completely blocked spermatogonial differentiation identical to vitamin A-deficient (VAD) mice; (2) the blockage of spermatogonial differentiation by impaired retinoid signaling resulted from an arrest of entry of the undifferentiated spermatogonia into S phase; and (3) retinoid signaling regulated spermatogonial differentiation through controlling expression of its direct target genes, including replication-dependent core histone genes. Taken together, our results demonstrate that the action of retinoid signaling on spermatogonial differentiation in vivo is direct through the spermatogonia itself, and provide the first evidence that this is mediated by regulation of expression of replication-dependent core histone genes.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
authors.forename: Cathryn
authors.initials: C
authors.lastname: Hogarth
authors.affiliation: CAS-MPG Partner Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA mgriswold@wsu.edu minghan@sibcb.ac.cn.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Griswold
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China mgriswold@wsu.edu minghan@sibcb.ac.cn.
authors.forename: Ming-Han
authors.initials: MH
authors.lastname: Tong
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D006657:Histones / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D000072482:Retinoic Acid Receptor alpha / Q000235:genetics* / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D013091:Spermatogenesis / Q000235:genetics*; D013093:Spermatogonia / Q000166:cytology* / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism; D014802:Vitamin A Deficiency
chemical_list: D006657:Histones; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin
keywords: Dominant-negative retinoic acid receptor; Replication-dependent core histone genes; Retinoic acid; Spermatogenesis; Spermatogonial differentiation; Testis