Canonical Wnt Signalling Requires the BMP Pathway to Inhibit Oligodendrocyte Maturation

Abstract

OLs (oligodendrocytes) are the myelinating cells of the CNS (central nervous system), wrapping axons in conductive sheathes to ensure effective transmission of neural signals. The regulation of OL development, from precursor to mature myelinating cell, is controlled by a variety of inhibitory and inductive signalling factors. The dorsal spinal cord contains signals that inhibit OL development, possibly to prevent premature and ectopic precursor differentiation. The Wnt and BMP (bone morphogenic protein) signalling pathways have been identified as dorsal spinal cord signals with overlapping temporal activity, and both have similar inhibitory effects on OL differentiation. Both these pathways feature prominently in many developmental processes and demyelinating events after injury, and they are known to interact in complex inductive, inhibitive and synergistic manners in many developing systems. The interaction between BMP and Wnt signalling in OL development, however, has not been extensively explored. In the present study, we examine the relationship between the canonical Wnt and BMP pathways. We use pharmacological and genetic paradigms to show that both Wnt3a and BMP4 will inhibit OL differentiation in vitro. We also show that when the canonical BMP signalling pathway is blocked, neither Wnt3a nor BMP4 have inhibitory effects on OL differentiation. In contrast, abrogating the Wnt signalling pathway does not alter the actions of BMP4 treatment. Our results indicate that the BMP signalling pathway is necessary for the canonical Wnt signalling pathway to exert its effects on OL development, but not vice versa, suggesting that Wnt signals upstream of BMP.