2. Academic Validation
  3. Primary cilia control oligodendrocyte precursor cell proliferation in white matter injury via Hedgehog-independent CREB signaling

Primary cilia control oligodendrocyte precursor cell proliferation in white matter injury via Hedgehog-independent CREB signaling

  • Cell Rep. 2023 Oct 17;42(10):113272. doi: 10.1016/j.celrep.2023.113272.
Kimberly K Hoi 1,  Wenlong Xia 1,  Ming Ming Wei 1,  Maria Jose Ulloa Navas 2,  Jose-Manuel Garcia Verdugo 2,  Maxence V Nachury 3,  Jeremy F Reiter 4,  Stephen P J Fancy 5
Affiliations

Affiliations

  • 1 Departments of Neurology and Pediatrics, Division of Neuroimmunology and Glial Biology, Newborn Brain Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
  • 2 Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, 46980 Paterna, Spain.
  • 3 Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 4 Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • 5 Departments of Neurology and Pediatrics, Division of Neuroimmunology and Glial Biology, Newborn Brain Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: [email protected].
PMID: 37858465 DOI: 10.1016/j.celrep.2023.113272
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.

Keywords

CP: Developmental biology; CP: Neuroscience; CREB; GPCR; Hedgehog; oligodendrocyte; oligodendrocyte precursor cell; primary cilia; proliferation; remyelination; white matter injury.

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