BMP4 signals via BMPR1 in OPCs to enhance oligodendrocyte differentiation and reduce astrogliogenesis in vitro.
A, Representative micrographs of immunostaining of differentiated OPC cultures for MBP and GFAP under untreated (Control) conditions, or following treatment with BMP4, LDN-193189 (LDN), or both BMP4 and LDN-193189 (LDN+BMP4). B, Quantification of cell phenotypic distribution for each condition based on GFAP expression and MBP+ morphology. MBP+ cells were classified as either mature (flattening of branched extracellular membrane) or immature (branched morphology but not fused layers). C, Quantification of the proportion of GFAP+ cells in the cultures. BMP4 significantly increased the proportion of GFAP+ cells compared with untreated (Control) cultures. While LDN-193189 (LDN) alone exerted no significant effect, pretreatment with LDN before BMP4 (LDN+BMP4) significantly abrogated effect of BMP4 on astrocytes. D, Quantification of the proportion of immature oligodendrocytes in the cultures. Treatment with BMP4 or LDN-193189 (LDN) exerted no significant effect, whereas pretreatment with LDN-193189 before BMP4 (LDN+BMP4) significantly increased the proportion of immature oligodendrocytes. E, Quantification of the proportion of mature oligodendrocytes in the cultures. Treatment with BMP4 significantly blocked OPC differentiation, whereas LDN-193189 (LDN) alone exerted no significant effect. Pretreatment with LDN before BMP4 (LDN+BMP4) significantly abrogated the effect of BMP4 on oligodendrocyte differentiation (N = 4 animals/group). ****p < 0.0001. Scale bar, 20 µm.