Fig. 1.

Activin receptor signaling is required for developmental myelination. a Diagram of activin receptor signaling: Acvr2a and Acvr2b are ligand-binding receptors that require Acvr1b to induce intracellular signallng. In PDGFRa-Cre; Acvr1b^fl/fl mice, the knockout of Acvr1b eliminates all activin receptor signaling from both ligand binding receptors. b Western blots of brain lysates from P16 Acvr1b^fl/fl and PDGFRa-Cre; Acvr1b^fl/fl mice (cerebellum) labeled for CNP (46 kDa) or MBP (14–21 kDa) with β-Actin as a loading control. c Images of corpus callosum, cerebellum [counterstained with Hoechst (blue)] and dorsal spinal cord in P16 Acvr1b^fl/fl and PDGFRa-Cre; Acvr1b^fl/fl mice immunostained for myelin protein MAG (green). Scale bar 25 μm. d Mean MAG intensity normalized to background ± s.e.m. in the corpus callosum of P16 Acvr1b^fl/fl (n = 4 mice), PDGFRa-Cre; Acvr1b^fl/+ (n = 4 mice) and PDGFRa-Cre; Acvr1b^fl/fl mice (n = 6 mice). Two-tailed Student’s t test, *P = 0.0211, **0.0018. e Mean number of myelinated fibers ± s.e.m. per field of toluidine-blue stained semi-thin resin sections of corpus callosum at P16 in Acvr1b^fl/fl and PDGFRa-Cre; Acvr1b^fl/fl mice (n = 3 mice per group). Two-tailed Student’s t test, **P = 0.0034. f Toluidine-blue stained semi-thin resin sections of corpus callosum in Acvr1b^fl/fl (left) and PDGFRa-Cre; Acvr1b^fl/fl mice (right), with expanded field of view (f(a) and f(b), respectively). Scale bar 20 μm. g Analysis of distribution of myelinated axons in relation to axon diameter, represented as proportion of myelinated axons only (from all diameters), in Acvr1b^fl/fl (magenta) and PDGFRa-Cre; Acvr1b^fl/fl mice (green) mice (n = 3 mice per genotype) overlaid with polynomial best-fit regression curves (R² = 0.8897, 0.8344, respectively). Kolmogorov–Smirnov test, **P = 0.002