Wnt signaling is sufficient to perturb oligodendrocyte maturation

Abstract

The development of oligodendrocytes, the myelinating cells of the central nervous system, is temporally and spatially controlled by local signaling factors acting as inducers or inhibitors. Dorsal spinal cord tissue has been shown to contain inhibitors of oligodendrogliogenesis, although their identity is not completely known. We have studied the actions of one family of dorsal signaling molecules, the Wnts, on oligodendrocyte development. Using tissue culture models, we have shown that canonical Wnt activity through β-catenin activation inhibits oligodendrocyte maturation, independently of precursor proliferation, cell death, or diversion to an alternate cell fate. Mice in which Wnt/β-catenin signaling was constitutively activated in cells of the oligodendrocyte lineage had equal numbers of oligodendrocyte precursors relative to control littermates, but delayed appearance of mature oligodendrocytes, myelin protein, and myelinated axons during development, although these differences largely disappeared by adulthood. These results indicate that activating the Wnt/β-catenin pathway delays the development of myelinating oligodendrocytes.