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

Autor: Cullen CL; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia., O'Rourke M; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia., Beasley SJ; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia., Auderset L; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia., Zhen Y; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia., Pepper RE; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia., Gasperini R; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.; School of Medicine, University of Tasmania, Hobart, Australia., Young KM; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
Jazyk: angličtina
Zdroj: Glia [Glia] 2021 May; Vol. 69 (5), pp. 1184-1203. Date of Electronic Publication: 2020 Dec 24.
DOI: 10.1002/glia.23957
Abstrakt: 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.
(© 2020 The Authors. Glia published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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