Kif3a deletion prevents primary cilia assembly on oligodendrocyte progenitor cells, reduces oligodendrogenesis and impairs fine motor function
| Autor: | Renee E Pepper, Megan O'Rourke, Carlie L. Cullen, Loic Auderset, Shannon J Beasley, Kaylene M. Young, Robert Gasperini, Yilan Zhen |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Kinesins Mice Transgenic Biology Kif3a Mice 03 medical and health sciences Cellular and Molecular Neuroscience Myelin primary cilia 0302 clinical medicine Growth factor receptor medicine Animals KIF3A Cilia Research Articles Oligodendrocyte Precursor Cells Cilium oligodendrocyte progenitor cell Cell Differentiation Cell cycle Oligodendrocyte Cell biology myelin Adult Stem Cells Oligodendroglia stomatognathic diseases 030104 developmental biology medicine.anatomical_structure nervous system Neurology Kinesin oligodendrocyte 030217 neurology & neurosurgery Research Article |
| Zdroj: | Glia |
| ISSN: | 1098-1136 0894-1491 |
| Popis: | 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. Main Points OPCs disassemble primary cilia upon cell cycle re‐entry.Deletion of Kif3a from OPCs prevents primary cilia assembly and reduces OPC proliferation.Deletion of Kif3a from adult OPCs in vivo reduces oligodendrogenesis and impairs motor function. |
| Databáze: | OpenAIRE |
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