title: Normal formation of a vertebrate body plan and loss of tissue maintenance in the absence of ezh2.
abstract: Polycomb group (PcG) proteins are transcriptional repressors of numerous genes, many of which regulate cell cycle progression or developmental processes. We used zebrafish to study Enhancer of zeste homolog 2 (Ezh2), the PcG protein responsible for placing the transcriptional repressive H3K27me3 mark. We identified a nonsense mutant of ezh2 and generated maternal zygotic (MZ) ezh2 mutant embryos. In contrast to knockout mice for PcG proteins, MZezh2 mutant embryos gastrulate seemingly normal, but die around 2 days post fertilization displaying pleiotropic phenotypes. Expression analyses indicated that genes important for early development are not turned off properly, revealing a regulatory role for Ezh2 during zygotic gene expression. In addition, we suggest that Ezh2 regulates maternal mRNA loading of zygotes. Analyses of tissues arising later in development, such as heart, liver, and pancreas, indicated that Ezh2 is required for maintenance of differentiated cell fates. Our data imply that the primary role of Ezh2 is to maintain tissues after tissue specification. Furthermore, our work indicates that Ezh2 is essential to sustain tissue integrity and to set up proper maternal mRNA contribution, and presents a novel and powerful tool to study how PcG proteins contribute to early vertebrate development.
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Bilge
authors.initials: B
authors.lastname: San
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Naomi D
authors.initials: ND
authors.lastname: Chrispijn
authors.affiliation: Hubrecht Institute, University Medical Centre Utrecht, Utrecht, The Netherlands.|Institute of Molecular Biology, Mainz, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Wittkopp
authors.affiliation: Radboud University, Faculty of Science, Department of Molecular Developmental Biology, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: van Heeringen
authors.affiliation: Hubrecht Institute, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Lagendijk
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Aben
authors.affiliation: Hubrecht Institute, University Medical Centre Utrecht, Utrecht, The Netherlands.|Medical Physiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Bakkers
authors.affiliation: Hubrecht Institute, University Medical Centre Utrecht, Utrecht, The Netherlands.|Institute of Molecular Biology, Mainz, Germany.
authors.forename: René F
authors.initials: RF
authors.lastname: Ketting
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.|Radboud University, Faculty of Science, Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.|Hubrecht Institute, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Leonie M
authors.initials: LM
authors.lastname: Kamminga
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development / Q000502:physiology; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000254:growth & development; D015870:Gene Expression; D005838:Genotype; D006321:Heart / Q000254:growth & development; D006657:Histones / Q000235:genetics / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5 / Q000235:genetics / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D059008:Time-Lapse Imaging; D015027:Zebrafish / Q000378:metabolism; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D015053:Zygote / Q000378:metabolism
chemical_list: D006657:Histones; D000072576:Homeobox Protein Nkx-2.5; C528182:Nkx2.5 protein, zebrafish; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein