Fig 1: Overexpression of Wnt2 in mPFC glutamatergic neurons alleviates myelin injury and improves cognition. Results of the a) Y‐maze and b) T‐maze tests showing the spontaneous alternation percentage in the control and Camk2a‐Wnt2 groups at 2 months after surgery. n = 15–16 per group. Results of the open field test showing c) the total distance travelled and d) time spent in the corner area and e) center area in the control and Camk2a‐Wnt2 groups at 2 months after surgery. n = 15–16 per group. f) Heatmaps generated from DTI axial views of FA acquired from the control and Camk2a‐Wnt2 groups at 2 months after surgery. g) Quantification of FA values in the corpus callosum in the control and Camk2a‐Wnt2 groups at 2 months after surgery. The measured values were normalized to the mean value of the control group. n = 11 per group. h) Representative images of Black‐gold staining and immunostaining of MBP and MAG in the corpus callosum in the control and Camk2a‐Wnt2 groups at 2 months after surgery. Scale bar: 200 µm. Quantification of i) Black‐gold staining and immunostaining of j) MBP and k) MAG in the corpus callosum in the control and Camk2a‐Wnt2 groups at 2 months after surgery. n = 4 per group. l) Representative TEM images of the corpus callosum in the control and Camk2a‐Wnt2 groups at 2 months after surgery. Scale bar: 1 µm. m) The percentage of myelinated axons in the corpus callosum in the control and Camk2a‐Wnt2 groups at 2 months after surgery. n = 4 per group. n) Scatterplots of the myelin g‐ratio as a function of the axon diameter in the corpus callosum in the control and Camk2a‐Wnt2 groups at 2 months after surgery. Axons were selected from 4 mice per group for measurement. n = 138 and n = 121 measured axons for each group, respectively. o) Representative immunostaining of CC1 and Olig2 in the corpus callosum in the control and Camk2a‐Wnt2 groups at 2 months after surgery. Scale bar: 50 µm. Density of p) CC1+Olig2+ cells and q) CC1−Olig2+ cells in the corpus callosum in the control and Camk2a‐Wnt2 groups at 2 months after surgery. n = 5 per group. r) Proportion of CC1+/Olig2+ cells in the corpus callosum in the control and Camk2a‐Wnt2 groups at 2 months after surgery. n = 5 per group. s) Immunoblot bands and t) quantification of MBP and u) MAG expression in OPCs in the control, T3, and T3+ rmWnt2 groups. The intensity of each immunoblot band was normalized to that of the β‐actin band. The measured values were normalized to the mean value of the control group. n = 3 per group. The data are presented as the mean ± SEM. p‐values were determined by Student's t‐test in (b–e), (i–k), (m), (p–r), and (t); by the Mann–Whitney test in (a), (g), and (n); and by 1‐way ANOVA with Tukey's post‐hoc analysis in (u). *p < 0.05, **p < 0.01, ***p < 0.001.