Fig. 5
Partial rescue of Schwann cell (SC) defects in Ep400ΔPNS mice by Tfap2a deletion. a–e Determination of Sox10-positive SCs (a) and the number of Sox2- (b), Oct6- (c), Krox20- (d), and Mbp-positive (e) subpopulations in sciatic nerve sections of control (black bars), Tfap2aΔPNS (dark gray bars), Ep400ΔPNS (white bars), and double knockout (dko, light gray bars) mice at P0, P9, P21, and 2 months (n = 3; mean values ± SEM). f–m Immunohistochemistry with antibodies against Mbp (f–i) and in situ hybridization with a Mpz-specific probe (j–m) on sciatic nerve sections from control, Tfap2aΔPNS, Ep400ΔPNS, and dko mice at P21. n–r Determination of mean g ratio (n), myelin debris (o), myelin outfoldings (p), nodal (q), and paranodal (r) length from ultrathin sciatic nerve sections of control (blue bars), Ep400ΔPNS (red bars), and dko (light gray bars) mice at P21 (mean values ± SEM, n = 3 in o–r and 100–200 axons in n). Values for control and Ep400ΔPNS mice are those shown in Fig. 1q and Supplementary Fig. 3s–v. s–u Comparison of Ki67-positive proliferating SCs (s), cleaved Caspase 3-positive apoptotic SCs (t), and Iba1-positive macrophages (u) in sciatic nerve sections of control (black bars), Ep400ΔPNS (white bars), and dko (light gray bars) mice at P0, P9, P21, and 2 months (n = 3; mean values ± SEM). Statistical significance was determined by analysis of variance (*P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001). Exact values are listed in Supplementary Tables 1, 4, 5, 9, and 11 and source data are provided as a Source Data file. v Model summarizing the proposed action of Ep400. In normal SCs, Ep400 helps to turn off expression of transcriptional regulatory genes active in the precursor (Tfap2a) and immature (Pax3, Sox2) SC stage by replacing H2A.Z-containing by H2A-containing nucleosomes at their transcriptional start site. In Ep400-deficient SCs, genes keep their H2A.Z-containing nucleosomes, remain aberrantly expressed, and interfere with the expression of Krox20 and the myelin genes
