The Hedgehog morphogen aroused an enormous interest since it was characterized as an essential signal for ventral patterning of the spinal cord two decades ago. The pathway is notably implicated in the initial appearance of the progenitors of oligodendrocytes (OPCs), the glial cells of the central nervous system which after maturation are responsible for axon myelination. In accordance with the requirement for Hedgehog signaling in ventral patterning, the earliest identifiable cells in the oligodendrocyte lineage are derived from the ventral ventricular zone of the developing spinal cord and brain. Here, we present the current knowledge about the involvement of Hedgehog signaling in the strict spatial and temporal regulation which characterizes the initiation and progression of the oligodendrocyte lineage. We notably describe the ability of the Hedgehog signaling to tightly orchestrate the appearance of specific combinations of genes in concert with other pathways. We document the molecular mechanisms controlling Hedgehog temporal activity during OPC specification. The contribution of the pathway to aspects of OPC development different from their specification is also highlighted especially in the optic nerve. Finally, we report the data demonstrating that Hedgehog signaling-dependency is not a universal situation for oligodendrocyte generation as evidenced in the dorsal spinal cord in contrast to the dorsal forebrain.

Myelination leads to the formation of myelin sheaths surrounding neuronal axons and is crucial for function, plasticity and repair of the central nervous system (CNS). It relies on the interaction of the axons and the oligodendrocytes: the glial cells producing CNS myelin. Here, we have investigated the role of a crucial component of the Sonic hedgehog (Shh) signalling pathway, the co-receptor Boc, in developmental and repairing myelination. During development, Boc mutant mice display a transient decrease in oligodendroglial cell density together with delayed myelination. Despite recovery of oligodendroglial cells at later stages, adult mutants still exhibit a lower production of myelin basic protein correlated with a significant decrease in the calibre of callosal axons and a reduced amount of the neurofilament NF-M. During myelin repair, the altered OPC differentiation observed in the mutant is reminiscent of the phenotype observed after blockade of Shh signalling. In addition, Boc mutant microglia/macrophages unexpectedly exhibit the apparent inability to transition from a highly to a faintly ramified morphology in vivo. Altogether, these results identify Boc as an important component of myelin formation and repair.