Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling

The transcription factor CREB (cAMP-response element binding protein) regulates differentiation, migration, survival and activity-dependent gene expression in the developing and mature nervous system. However, its specific role in the proliferation of embryonic neural progenitors is still not comple...

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Main Authors: Parlato, Rosanna, Mandl, Claudia, Hölzl-Wenig, Gabriele, Liss, Birgit, Tucker, Kerry L, Ciccolini, Francesca
Format: Online
Language:English
Published: Taylor & Francis 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973597/
id pubmed-4973597
recordtype oai_dc
spelling pubmed-49735972016-08-08 Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling Parlato, Rosanna Mandl, Claudia Hölzl-Wenig, Gabriele Liss, Birgit Tucker, Kerry L Ciccolini, Francesca Research Paper The transcription factor CREB (cAMP-response element binding protein) regulates differentiation, migration, survival and activity-dependent gene expression in the developing and mature nervous system. However, its specific role in the proliferation of embryonic neural progenitors is still not completely understood. Here we investigated how CREB regulates proliferation of mouse embryonic neural progenitors by a conditional mutant lacking Creb gene in neural progenitors. In parallel, we explored possible compensatory effects by the genetic ablation of another member of the same gene family, the cAMP-responsive element modulator (Crem). We show that CREB loss differentially impaired the proliferation, clonogenic potential and self-renewal of precursors derived from the ganglionic eminence (GE), in comparison to those derived from the cortex. This phenotype was associated with a specific reduction of histone acetylation in the GE of CREB mutant mice, and this reduction was rescued in vivo by inhibition of histone deacetylation. These observations indicate that the impaired proliferation could be caused by a reduced acetyltransferase activity in Creb conditional knock-out mice. These findings support a crucial role of CREB in controlling embryonic neurogenesis and propose a novel mechanism by which CREB regulates embryonic neural development. Taylor & Francis 2014-11-26 /pmc/articles/PMC4973597/ /pubmed/27504469 http://dx.doi.org/10.4161/23262125.2014.970883 Text en © 2014 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Parlato, Rosanna
Mandl, Claudia
Hölzl-Wenig, Gabriele
Liss, Birgit
Tucker, Kerry L
Ciccolini, Francesca
spellingShingle Parlato, Rosanna
Mandl, Claudia
Hölzl-Wenig, Gabriele
Liss, Birgit
Tucker, Kerry L
Ciccolini, Francesca
Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling
author_facet Parlato, Rosanna
Mandl, Claudia
Hölzl-Wenig, Gabriele
Liss, Birgit
Tucker, Kerry L
Ciccolini, Francesca
author_sort Parlato, Rosanna
title Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling
title_short Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling
title_full Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling
title_fullStr Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling
title_full_unstemmed Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling
title_sort regulation of proliferation and histone acetylation in embryonic neural precursors by creb/crem signaling
description The transcription factor CREB (cAMP-response element binding protein) regulates differentiation, migration, survival and activity-dependent gene expression in the developing and mature nervous system. However, its specific role in the proliferation of embryonic neural progenitors is still not completely understood. Here we investigated how CREB regulates proliferation of mouse embryonic neural progenitors by a conditional mutant lacking Creb gene in neural progenitors. In parallel, we explored possible compensatory effects by the genetic ablation of another member of the same gene family, the cAMP-responsive element modulator (Crem). We show that CREB loss differentially impaired the proliferation, clonogenic potential and self-renewal of precursors derived from the ganglionic eminence (GE), in comparison to those derived from the cortex. This phenotype was associated with a specific reduction of histone acetylation in the GE of CREB mutant mice, and this reduction was rescued in vivo by inhibition of histone deacetylation. These observations indicate that the impaired proliferation could be caused by a reduced acetyltransferase activity in Creb conditional knock-out mice. These findings support a crucial role of CREB in controlling embryonic neurogenesis and propose a novel mechanism by which CREB regulates embryonic neural development.
publisher Taylor & Francis
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973597/
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