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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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/ |
_version_ |
1613621415537278976 |