title: EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21.
abstract: The function of EZH2 as a transcription repressor is well characterized. However, its role during vertebrate development is still poorly understood, particularly in neurogenesis. Here, we uncover the role of EZH2 in controlling the integrity of the neural tube and allowing proper progenitor proliferation. We demonstrate that knocking down the EZH2 in chick embryo neural tubes unexpectedly disrupts the neuroepithelium (NE) structure, correlating with alteration of the Rho pathway, and reduces neural progenitor proliferation. Moreover, we use transcriptional profiling and functional assays to show that EZH2-mediated repression of p21(WAF1/CIP1) contributes to both processes. Accordingly, overexpression of cytoplasmic p21(WAF1/CIP1) induces NE structural alterations and p21(WAF1/CIP1) suppression rescues proliferation defects and partially compensates for the structural alterations and the Rho activity. Overall, our findings describe a new role of EZH2 in controlling the NE integrity in the neural tube to allow proper progenitor proliferation.
authors.affiliation: Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain.
authors.forename: Naiara
authors.initials: N
authors.lastname: Akizu
authors.affiliation: Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain.
authors.forename: María Alejandra
authors.initials: MA
authors.lastname: García
authors.affiliation: Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain.
authors.forename: Conchi
authors.initials: C
authors.lastname: Estarás
authors.affiliation: Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Fueyo
authors.affiliation: Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Badosa
authors.affiliation: Vall d'Hebron Institute of Research (VHIR), Passeig de la Vall d'Hebron, 119, Barcelona 08035, Spain Institut Català per la Recerca i Estudis Avançats (ICREA), Barcelona 08018, Spain mmbbmc@ibmb.csic.es.
authors.forename: Xavier
authors.initials: X
authors.lastname: de la Cruz
authors.affiliation: Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain xavhir@gmail.com.
authors.forename: Marian A
authors.identifier: http://orcid.org/0000-0003-0173-0964
authors.initials: MA
authors.lastname: Martínez-Balbás
mesh_terms: D000818:Animals; D016764:Cell Polarity; D049109:Cell Proliferation; D002642:Chick Embryo; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D054259:Neural Tube / Q000166:cytology / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000166:cytology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D012097:Repressor Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: EZH2; gene silencing; histone methylation; neural development; neuroblast proliferation