title: The polycomb component Ring1B regulates the timed termination of subcerebral projection neuron production during mouse neocortical development.
abstract: In the developing neocortex, neural precursor cells (NPCs) sequentially generate various neuronal subtypes in a defined order. Although the precise timing of the NPC fate switches is essential for determining the number of neurons of each subtype and for precisely generating the cortical layer structure, the molecular mechanisms underlying these switches are largely unknown. Here, we show that epigenetic regulation through Ring1B, an essential component of polycomb group (PcG) complex proteins, plays a key role in terminating NPC-mediated production of subcerebral projection neurons (SCPNs). The level of histone H3 residue K27 trimethylation at and Ring1B binding to the promoter of Fezf2, a fate determinant of SCPNs, increased in NPCs as Fezf2 expression decreased. Moreover, deletion of Ring1B in NPCs, but not in postmitotic neurons, prolonged the expression of Fezf2 and the generation of SCPNs that were positive for CTIP2. These results indicate that Ring1B mediates the timed termination of Fezf2 expression and thereby regulates the number of SCPNs.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Morimoto-Suzki
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan yhira@iam.u-tokyo.ac.jp ygotoh@mol.f.u-tokyo.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hirabayashi
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Tyssowski
authors.affiliation: RIKEN Center for Allergy and Immunology, Kanagawa, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shinga
authors.affiliation: RIKEN Center for Allergy and Immunology, Kanagawa, Japan Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Vidal
authors.affiliation: RIKEN Center for Allergy and Immunology, Kanagawa, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan yhira@iam.u-tokyo.ac.jp ygotoh@mol.f.u-tokyo.ac.jp.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Gotoh
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000502:physiology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D019579:Neocortex / Q000196:embryology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: C511143:Bcl11b protein, mouse; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C412364:Zfp312 protein, mouse; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D001973:Bromodeoxyuridine
keywords: Fezf2; Neocortical development; Neural precursor cell; Neural stem cell; Polycomb