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Kif3a deletion prevents primary cilia assembly on oligodendrocyte progenitor cells, reduces oligodendrogenesis and impairs fine motor function

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Cullen, CL ORCID: 0000-0001-6929-6258, O'Rourke, M, Beasley, SJ ORCID: 0000-0002-8706-5725, Auderset, L, Zhen, Y, Pepper, RE, Gasperini, R ORCID: 0000-0001-6859-1247 and Young, KM ORCID: 0000-0002-1686-3463 2020 , 'Kif3a deletion prevents primary cilia assembly on oligodendrocyte progenitor cells, reduces oligodendrogenesis and impairs fine motor function' , Glia , pp. 1-20 , doi: 10.1002/glia.23957.

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Abstract

Primary cilia are small microtubule-based organelles capable of transducing signals from growth factor receptors embedded in the cilia membrane. Developmentally, oligodendrocyte progenitor cells (OPCs) express genes associated with primary cilia assembly, disassembly, and signaling, however, the importance of primary cilia for adult myelination has not been explored. We show that OPCs are ciliated in vitro and in vivo, and that they disassemble their primary cilia as they progress through the cell cycle. OPC primary cilia are also disassembled as OPCs differentiate into oligodendrocytes. When kinesin family member 3a (Kif3a), a gene critical for primary cilium assembly, was conditionally deleted from adult OPCs in vivo (Pdgfrα-CreER™:: Kif3a fl/fl transgenic mice), OPCs failed to assemble primary cilia. Kif3a-deletion was also associated with reduced OPC proliferation and oligodendrogenesis in the corpus callosum and motor cortex and a progressive impairment of fine motor coordination.

Item Type: Article
Authors/Creators:Cullen, CL and O'Rourke, M and Beasley, SJ and Auderset, L and Zhen, Y and Pepper, RE and Gasperini, R and Young, KM
Keywords: Kif3a, myelin, oligodendrocyte, oligodendrocyte progenitor cell, primary cilia
Journal or Publication Title: Glia
Publisher: Wiley-Liss
ISSN: 0894-1491
DOI / ID Number: 10.1002/glia.23957
Copyright Information:

Copyright 2020 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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