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PMID: 27248655 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21.

Open biology ·Vol. 6 ·No. 4 ·2016-04-00 ·Pages 150227

Akizu N, García MA, Estarás C, Fueyo R, Badosa C, de la Cruz X, Martínez-Balbás MA

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.

Keywords
EZH2 gene silencing histone methylation neural development neuroblast proliferation
MeSH Terms
Animals Cell Polarity Cell Proliferation Chick Embryo Cyclin-Dependent Kinase Inhibitor p21/genetics,metabolism Enhancer of Zeste Homolog 2 Protein/metabolism Gene Expression Regulation, Developmental Humans Neural Stem Cells/cytology,metabolism Neural Tube/cytology,metabolism Neuroepithelial Cells/cytology,metabolism Promoter Regions, Genetic/genetics Repressor Proteins/metabolism
Chemicals
Cyclin-Dependent Kinase Inhibitor p21 Repressor Proteins Enhancer of Zeste Homolog 2 Protein
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Akizu Naiara
Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain.
García María Alejandra
Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain.
Estarás Conchi
Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain.
Fueyo Raquel
Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain.
Badosa Carmen
Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain.
de la Cruz Xavier
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.
Martínez-Balbás Marian A ORCID
Department of Molecular Genomics, Instituto de Biología Molecular de Barcelona (IBMB), Consejo Superior de Investigaciones Científicas (CSIC), Barcelona 08028, Spain xavhir@gmail.com.
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Article Info
Journal
Open biology
Abbr.
Open Biol
ISSN
2046-2441
DOI
10.1098/rsob.150227
Email
mmbbmc@ibmb.csic.es
xavhir@gmail.com
Published
2016-04-00
Epub
2016-00-20
Pages
150227
Language
English
Region
England
NLM ID
101580419
PMCID
PMC4852452
Subset
IM
External Links
PubMed source DOI: 10.1098/rsob.150227 PMC Full Text View journal details
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