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

Citation

Cullen, CL and O'Rourke, M and Beasley, SJ and Auderset, L and Zhen, Y and Pepper, RE and Gasperini, R and Young, KM, Kif3a deletion prevents primary cilia assembly on oligodendrocyte progenitor cells, reduces oligodendrogenesis and impairs fine motor function, Glia pp. 1-20. ISSN 0894-1491 (2020) [Refereed Article]


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DOI: doi:10.1002/glia.23957

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 Details

Item Type:Refereed Article
Keywords:Kif3a, myelin, oligodendrocyte, oligodendrocyte progenitor cell, primary cilia
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biomedical and clinical sciences
UTAS Author:Cullen, CL (Dr Carlie Cullen)
UTAS Author:O'Rourke, M (Ms Megan O'Rourke)
UTAS Author:Beasley, SJ (Dr Shannon Beasley)
UTAS Author:Auderset, L (Mr Loic Auderset)
UTAS Author:Zhen, Y (Miss Yilan Zhen)
UTAS Author:Pepper, RE (Miss Renee Pepper)
UTAS Author:Gasperini, R (Dr Rob Gasperini)
UTAS Author:Young, KM (Associate Professor Kaylene Young)
ID Code:142286
Year Published:2020
Funding Support:Australian Research Council (DP180101494)
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-01-05
Last Modified:2021-01-14
Downloads:0

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