1. Primary cilia control oligodendrocyte precursor cell proliferation in white matter injury via Hedgehog-independent CREB signaling.
- Author
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Hoi, Kimberly, Xia, Wenlong, Wei, Ming, Ulloa Navas, Maria, Garcia Verdugo, Jose-Manuel, Reiter, Jeremy, Fancy, Stephen, and Nachury, Maxence
- Subjects
CP: Developmental biology ,CP: Neuroscience ,CREB ,GPCR ,Hedgehog ,oligodendrocyte ,oligodendrocyte precursor cell ,primary cilia ,proliferation ,remyelination ,white matter injury ,Oligodendrocyte Precursor Cells ,Cilia ,White Matter ,Hedgehog Proteins ,Oligodendroglia ,Myelin Sheath ,Cyclic AMP Response Element-Binding Protein ,Cell Proliferation ,Cell Differentiation - Abstract
Remyelination after white matter injury (WMI) often fails in diseases such as multiple sclerosis because of improper recruitment and repopulation of oligodendrocyte precursor cells (OPCs) in lesions. How OPCs elicit specific intracellular programs in response to a chemically and mechanically diverse environment to properly regenerate myelin remains unclear. OPCs construct primary cilia, specialized signaling compartments that transduce Hedgehog (Hh) and G-protein-coupled receptor (GPCR) signals. We investigated the role of primary cilia in the OPC response to WMI. Removing cilia from OPCs genetically via deletion of Ift88 results in OPCs failing to repopulate WMI lesions because of reduced proliferation. Interestingly, loss of cilia does not affect Hh signaling in OPCs or their responsiveness to Hh signals but instead leads to dysfunctional cyclic AMP (cAMP)-dependent cAMP response element-binding protein (CREB)-mediated transcription. Because inhibition of CREB activity in OPCs reduces proliferation, we propose that a GPCR/cAMP/CREB signaling axis initiated at OPC cilia orchestrates OPC proliferation during development and in response to WMI.
- Published
- 2023