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Recent studies have highlighted that MOLs are heterogeneous; however, how MOL subpopulations are specified and balanced in physiological settings is poorly understood. Previous works have demonstrated an essential role of the small GTPases R\u2010Ras1 and R\u2010Ras2 in the survival and myelination of oligodendrocytes. In this study, we aimed to determine how R\u2010Ras1 and R\u2010Ras2 contribute to the heterogeneity of MOL subpopulations. Our results evidence that R\u2010Ras1 and R\u2010Ras2 affect specification into the distinct subpopulations MOL1, MOL2, and MOL5\/6, which in turn vary in their dependence of these GTPases. In R\u2010Ras1 and\/or R\u2010Ras2 mutant mice, we observed an increase in the MOL1 subpopulation and a decrease in the MOL2 and MOL5\/6 subpopulations. We identified R\u2010Ras1 and R\u2010Ras2 as key elements in balancing the heterogeneity of MOLs. Our results contribute to the understanding of the molecular mechanisms underlying the heterogeneity of MOLs and the myelination processes, which is crucial for innovating regenerative therapies for nervous system disorders.<\/jats:p>","DOI":"10.1002\/glia.24643","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T09:09:53Z","timestamp":1732007393000},"page":"701-719","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["R\u2010Ras1 and R\u2010Ras2 regulate mature oligodendrocyte subpopulations"],"prefix":"10.1002","volume":"73","author":[{"given":"Berta","family":"Alcover\u2010Sanchez","sequence":"first","affiliation":[{"name":"Centro de Biologia Molecular Severo Ochoa (CBM) CSIC Universidad Autonoma de Madrid  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo","family":"Garcia\u2010Martin","sequence":"additional","affiliation":[{"name":"Centro de 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