Sonic hedgehog is required during an early phase of oligodendrocyte development in mammalian brain

Oligodendrocyte precursor development in the embryonic spinal cord is thoug ht to be regulated by the secreted signal, Sonic hedgehog (Shh). Such precu rsors can be identified by the expression of Olig genes, encoding basic hel ix-loop-helix factors, in the spinal cord and brain. However, the signaling pathways that govern oligodendrocyte precursor (OLP) development in the ro stral central nervous system are poorly understood. Here, we show that Shh is required for oligodendrocyte development in the mouse forebrain and spin al cord, and that Shh proteins are both necessary and sufficient for OLP pr oduction in cortical neuroepithelial cultures. Moreover, adenovirus-mediate d Olig1 ectopic expression can promote OLP formation independent of Shh act ivity. Our results demonstrate essential functions for Shh during early pha ses of oligodendrocyte development in the mammalian central nervous system. They further suggest that a key role of Shh signaling is activation of Oli g genes.