title: Regulation of proliferation and histone acetylation in embryonic neural precursors by CREB/CREM signaling.
abstract: 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.
authors: Institute of Applied Physiology; University of Ulm; Ulm, Germany; Dept. of Molecular Biology of the Cell I; DKFZ-ZMBH Alliance; German Cancer Research Center; Heidelberg, Germany; Institute of Anatomy and Cell Biology; Interdisciplinary Center for Neurosciences (IZN); University of Heidelberg; Heidelberg, Germany.
authors: Rosanna
authors: R
authors: Parlato
authors: Department of Neurobiology; Interdisciplinary Center for Neurosciences (IZN); University of Heidelberg ; Heidelberg, Germany.
authors: Claudia
authors: C
authors: Mandl
authors: Department of Neurobiology; Interdisciplinary Center for Neurosciences (IZN); University of Heidelberg ; Heidelberg, Germany.
authors: Gabriele
authors: G
authors: Hölzl-Wenig
authors: Institute of Applied Physiology; University of Ulm ; Ulm, Germany.
authors: Birgit
authors: B
authors: Liss
authors: Institute of Anatomy and Cell Biology; Interdisciplinary Center for Neurosciences (IZN); University of Heidelberg; Heidelberg, Germany; Kerry L Tucker's current affiliation is the Center for Excellence in the Neurosciences, Dept. of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME, USA.
authors: Kerry L
authors: KL
authors: Tucker
authors: Department of Neurobiology; Interdisciplinary Center for Neurosciences (IZN); University of Heidelberg ; Heidelberg, Germany.
authors: Francesca
authors: F
authors: Ciccolini
keywords: CBP; CREB; Ganglionic eminence; histone acetylation; proliferation