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. 2022 Dec 14;613(7942):120–129. doi: 10.1038/s41586-022-05534-y

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© The Author(s) 2022, corrected publication 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Extended Data Fig. 7 — a) Adult FIRE^+/+ mice were fed the CSF1R inhibitor PLX5622 in the diet from 2 to 3 months of age. b) Representative images of IBA1+ cells (magenta) in the corpus callosum of 3-month old FIRE^+/+ mice on normal diet versus PLX5622 (PLX) diet from 2 to 3 months of age. Scale bar, 25 µm. c) Density of IBA1+ cells/mm² ± s.e.m. in FIRE^+/+ mice on normal diet versus PLX diet at 3 months of age. n = 5 mice on normal diet and 3 mice on PLX diet, ***P = 0.0004, 2-tailed unpaired Student’s t-test, d) Representative images of hypermyelination in the corpus callosum following PLX administration from 2 to 3 months of age. Scale bar, 1 µm. e) Representative images of enlarged inner tongues (orange) and thicker myelin (asterisks) following PLX administration from 2 to 3 months of age. Scale bar, 1 µm. f) Inner tongue thickness (µm) versus axon diameter in FIRE^+/+ mice on normal diet or PLX diet from 2 to 3 months of age. n = 100 axons/mouse. n = 3 mice on normal diet and 4 mice on PLX diet. ***P < 0.0001, simple linear regression of intercepts. g) Myelin thickness (µm) versus axon diameter in FIRE^+/+ mice on normal diet or PLX diet from 2 to 3 months of age. n = 100 axons per mouse. n = 5 mice on normal diet and 3 mice on PLX diet. ***P < 0.0001, simple linear regression of slopes. h) Images of mature oligodendrocytes co-expressing OLIG2 (white) and CC1 (magenta) in FIRE^+/+ mice on normal diet or PLX diet from 2 to 3 months of age. Scale bar, 75 µm. i) Mean OLIG2+ CC1+ cells per mm² ± s.e.m. in FIRE^+/+ mice on normal diet or PLX diet from 2 to 3 months of age. Non-significant, P = 0.3645, 2-tailed unpaired Student’s t-test. Mean proportion of cells of the oligodendrocyte lineage (OLIG2+) which are mature (CC1+; black) or immature (CC1-; grey) ± s.e.m at 3 months. Non-significant, CC1+: P = 0.3779; CC1-: P = 0.3779, 1-way ANOVA with Tukey’s multiple comparisons test. n = 5 mice on normal diet and 3 mice on PLX diet. j) Adult FIRE^+/+ mice were fed the CSF1R inhibitor PLX5622 in the diet from 5 to 6-months of age. k) Images of demyelination in the corpus callosum of 6-month-old FIRE^+/+ mice (asterisks) following PLX administration from 5 to 6-months of age. Scale bar, 1 µm. l) Mean number of myelinated axons ± s.e.m. in of FIRE^+/+ mice on normal diet versus PLX diet from 5 to 6-months of age. n = 3 mice/group. **P = 0.0024, 2-tailed unpaired Student’s t-test.

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