PMID- 27940202 OWN - NLM STAT- MEDLINE DCOM- 20180227 LR - 20191210 IS - 1095-953X (Electronic) IS - 0969-9961 (Linking) VI - 98 DP - 2017 Feb TI - The intellectual disability protein PAK3 regulates oligodendrocyte precursor cell differentiation. PG - 137-148 LID - S0969-9961(16)30285-6 [pii] LID - 10.1016/j.nbd.2016.12.004 [doi] AB - Oligodendrocyte and myelin deficits have been reported in mental/psychiatric diseases. The p21-activated kinase 3 (PAK3), a serine/threonine kinase, whose activity is stimulated by the binding of active Rac and Cdc42 GTPases is affected in these pathologies. Indeed, many mutations of Pak3 gene have been described in non-syndromic intellectual disability diseases. Pak3 is expressed mainly in the brain where its role has been investigated in neurons but not in glial cells. Here, we showed that PAK3 is highly expressed in oligodendrocyte precursors (OPCs) and its expression decreases in mature oligodendrocytes. In the developing white matter of the Pak3 knockout mice, we found defects of oligodendrocyte differentiation in the corpus callosum and to a lesser extent in the anterior commissure, which were compensated at the adult stage. In vitro experiments in OPC cultures, derived from Pak3 knockout and wild type brains, support a developmental and cell-autonomous role for PAK3 in regulating OPC differentiation into mature oligodendrocytes. Moreover, we did not detect any obvious alterations of the proliferation or migration of Pak3 null OPCs compared to wild type. Overall, our data highlight PAK3 as a new regulator of OPC differentiation. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Maglorius Renkilaraj, Majistor Raj Luxman AU - Maglorius Renkilaraj MRL AD - Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005 Paris, France. FAU - Baudouin, Lucas AU - Baudouin L AD - Sorbonne Universites, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle epiniere, F-75013 Paris, France. FAU - Wells, Claire M AU - Wells CM AD - Division of Cancer Studies, King's College London, UK. FAU - Doulazmi, Mohamed AU - Doulazmi M AD - Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Adaptation Biologique et vieillissement, F-75005 Paris, France. FAU - Wehrle, Rosine AU - Wehrle R AD - Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005 Paris, France. FAU - Cannaya, Vidjeacoumary AU - Cannaya V AD - Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005 Paris, France. FAU - Bachelin, Corinne AU - Bachelin C AD - Sorbonne Universites, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle epiniere, F-75013 Paris, France. FAU - Barnier, Jean-Vianney AU - Barnier JV AD - Institute of Neuroscience Paris-Saclay, CNRS-Universite Paris-Sud, UMR9197, F-91405 Orsay, France. FAU - Jia, Zhengping AU - Jia Z AD - Neurosciences & Mental Health, The Hospital for Sick Children, and Department of Physiology, Faculty of Medicine, University of Toronto, 555 University, Toronto, Ontario M5G 1X8, Canada. FAU - Nait Oumesmar, Brahim AU - Nait Oumesmar B AD - Sorbonne Universites, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle epiniere, F-75013 Paris, France. FAU - Dusart, Isabelle AU - Dusart I AD - Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005 Paris, France. FAU - Bouslama-Oueghlani, Lamia AU - Bouslama-Oueghlani L AD - Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005 Paris, France; Sorbonne Universites, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle epiniere, F-75013 Paris, France. Electronic address: lamia.bouslama@upmc.fr. LA - eng PT - Journal Article DEP - 20161206 PL - United States TA - Neurobiol Dis JT - Neurobiology of disease JID - 9500169 RN - EC 2.7.11.1 (Pak3 protein, mouse) RN - EC 2.7.11.1 (p21-Activated Kinases) SB - IM MH - Animals MH - Anterior Commissure, Brain/cytology/growth & development/metabolism MH - Cell Differentiation/*physiology MH - Cell Movement/physiology MH - Cells, Cultured MH - Corpus Callosum/cytology/growth & development/metabolism MH - Male MH - Mice, Knockout MH - Neural Stem Cells/cytology/*metabolism MH - Oligodendroglia/cytology/*metabolism MH - White Matter/cytology/growth & development/metabolism MH - p21-Activated Kinases/genetics/*metabolism OTO - NOTNLM OT - Development OT - Differentiation OT - Intellectual disability OT - Myelin OT - OPC OT - Oligodendrocyte OT - PAK3 EDAT- 2016/12/13 06:00 MHDA- 2018/02/28 06:00 CRDT- 2016/12/13 06:00 PHST- 2016/04/26 00:00 [received] PHST- 2016/11/04 00:00 [revised] PHST- 2016/12/02 00:00 [accepted] PHST- 2016/12/13 06:00 [pubmed] PHST- 2018/02/28 06:00 [medline] PHST- 2016/12/13 06:00 [entrez] AID - S0969-9961(16)30285-6 [pii] AID - 10.1016/j.nbd.2016.12.004 [doi] PST - ppublish SO - Neurobiol Dis. 2017 Feb;98:137-148. doi: 10.1016/j.nbd.2016.12.004. Epub 2016 Dec 6.