Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Functions of HDAC1 and HDAC2 in Schwann cells during postnatal


ABSTRACT: The aim of our study is to determine the functions of histone deacetylases (HDACs) 1 and 2 in Schwann cells during postnatal development of the peripheral nervous system (PNS). Schwann cells are the myelinating glial cells of the PNS. At birth, mouse sciatic nerves mature in 2 subsequent phases: 1/ big caliber axons get sorted into a 1 to 1 relationship with Schwann cells, 2/ Schwann cells build a myelin sheath around sorted axons. In mice where both HDAC1 & HDAC2 have been specifically knocked out in Schwann cells, both phases are impaired. HDACs are chromatin remodeling enzymes, they can thus alter gene expression directly. We want to identify which genes controlled by HDAC1 and HDAC2 in Schwann cells are necessary for the maturation of sciatic nerves. Because HDAC1 and HDAC2 can compensate for each other loss to some extend, we will first analyze changes of gene expression in HDAC1/HDAC2 double KO animals. We expect to gain critical insights into the molecular mechanisms controlling Schwann cell differentiation and myelination. This knowledge is of key importance for the success of regenerative medicine in peripheral neuropathies, nerve tumors, and transplantation paradigms in non-regenerative CNS lesions and in large PNS injuries. 3 double knockout mutants for HDAC1 and HDAC2 and 3 control littermates were analyzed. Tissues analyzed: sciatic nerves of 2 day-old mouse pups

ORGANISM(S): Mus musculus

SUBMITTER: Ueli Suter 

PROVIDER: E-GEOD-27451 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

HDAC1 and HDAC2 control the transcriptional program of myelination and the survival of Schwann cells.

Jacob Claire C   Christen Carlos N CN   Pereira Jorge A JA   Somandin Christian C   Baggiolini Arianna A   Lötscher Pirmin P   Ozçelik Murat M   Tricaud Nicolas N   Meijer Dies D   Yamaguchi Teppei T   Matthias Patrick P   Suter Ueli U  

Nature neuroscience 20110320 4


Histone deacetylases (HDACs) are major epigenetic regulators. We show that HDAC1 and HDAC2 functions are critical for myelination of the peripheral nervous system. Using mouse genetics, we have ablated Hdac1 and Hdac2 specifically in Schwann cells, resulting in massive Schwann cell loss and virtual absence of myelin in mutant sciatic nerves. Expression of Sox10 and Krox20, the main transcriptional regulators of Schwann cell myelination, was greatly reduced. We demonstrate that in Schwann cells,  ...[more]

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