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U.S.A."],"published-print":{"date-parts":[[2024,3,19]]},"abstract":"<jats:p>Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)\u2014a transcription factor known to regulate expression of actin and actin regulators in other cell types\u2014as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the mechanistic role of SRF in oligodendrocyte lineage cells. Here, we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in oligodendrocyte precursor cells and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Surprisingly, oligodendrocyte-restricted loss of SRF results in upregulation of gene signatures associated with aging and neurodegenerative diseases. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies an essential pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.<\/jats:p>","DOI":"10.1073\/pnas.2307250121","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T13:50:25Z","timestamp":1710424225000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination"],"prefix":"10.1073","volume":"121","author":[{"given":"Tal","family":"Iram","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4181-5372","authenticated-orcid":false,"given":"Miguel A.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1354-5486","authenticated-orcid":false,"given":"J\u00e9r\u00e9my","family":"Amand","sequence":"additional","affiliation":[{"name":"Department of Clinical Bioinformatics, Helmholtz Institute for Pharmaceutical Research Saarland\u2013Helmholtz Centre for Infection Research, Saarland University Campus, Saarbr\u00fccken 66123, Germany"},{"name":"Clinical Bioinformatics, Saarland University, Saarbr\u00fccken 66123, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achint","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0068-5217","authenticated-orcid":false,"given":"Micaiah","family":"Atkins","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manasi","family":"Iyer","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mable","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Ambiel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7143-0118","authenticated-orcid":false,"given":"Danielle M.","family":"Jorgens","sequence":"additional","affiliation":[{"name":"Electron Microscope Laboratory, University of California, Berkeley, CA 94720"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5361-0895","authenticated-orcid":false,"given":"Andreas","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Clinical Bioinformatics, Helmholtz Institute for Pharmaceutical Research Saarland\u2013Helmholtz Centre for Infection Research, Saarland University Campus, Saarbr\u00fccken 66123, Germany"},{"name":"Clinical Bioinformatics, Saarland University, Saarbr\u00fccken 66123, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Wyss-Coray","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Wu Tsai Neurosciences Institute, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8223-3750","authenticated-orcid":false,"given":"Fabian","family":"Kern","sequence":"additional","affiliation":[{"name":"Department of Clinical Bioinformatics, Helmholtz Institute for Pharmaceutical Research Saarland\u2013Helmholtz Centre for Infection Research, Saarland University Campus, Saarbr\u00fccken 66123, Germany"},{"name":"Clinical Bioinformatics, Saarland University, Saarbr\u00fccken 66123, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4706-2538","authenticated-orcid":false,"given":"J. 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