title: The intellectual disability protein PAK3 regulates oligodendrocyte precursor cell differentiation.
abstract: 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.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005 Paris, France.
authors.forename: Majistor Raj Luxman
authors.initials: MRL
authors.lastname: Maglorius Renkilaraj
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013 Paris, France.
authors.forename: Lucas
authors.initials: L
authors.lastname: Baudouin
authors.affiliation: Division of Cancer Studies, King's College London, UK.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Wells
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Adaptation Biologique et vieillissement, F-75005 Paris, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Doulazmi
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005 Paris, France.
authors.forename: Rosine
authors.initials: R
authors.lastname: Wehrlé
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005 Paris, France.
authors.forename: Vidjeacoumary
authors.initials: V
authors.lastname: Cannaya
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013 Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Bachelin
authors.affiliation: Institute of Neuroscience Paris-Saclay, CNRS-Université Paris-Sud, UMR9197, F-91405 Orsay, France.
authors.forename: Jean-Vianney
authors.initials: JV
authors.lastname: Barnier
authors.affiliation: 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.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013 Paris, France.
authors.forename: Brahim
authors.initials: B
authors.lastname: Nait Oumesmar
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005 Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dusart
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, F-75005 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle épinière, F-75013 Paris, France. Electronic address: lamia.bouslama@upmc.fr.
authors.forename: Lamia
authors.initials: L
authors.lastname: Bouslama-Oueghlani
mesh_terms: D000818:Animals; D066240:Anterior Commissure, Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D066127:White Matter / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C515912:Pak3 protein, mouse; D054462:p21-Activated Kinases
keywords: Development; Differentiation; Intellectual disability; Myelin; OPC; Oligodendrocyte; PAK3