Sonic hedgehog-regulateld oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system

During development, basic helix-loop-helix (bHLH) proteins regulate formati on of neurons from multipotent progenitor cells. However, bHLH factors link ed to gliogenesis have not been described. We have isolated a pair of oligo dendrocyte lineage genes (Olg-1 and Olg-2) that encode bHLH proteins and ar e tightly associated with development of oligodendrocytes in the vertebrate central nervous system (CNS). Ectopic expression of Olg-1 in rat cortical progenitor cell cultures promotes formation of oligodendrocyte precursors. In developing mouse embryos, Olg gene expression overlaps but precedes the earliest known markers of the oligodendrocyte lineage. Olg genes are expres sed at the tetencephalon-diencephalon border and adjacent to the floor plat e, a source of the secreted signaling molecule Sonic hedgehog (Shh). Gain- and loss-of-function analyses in transgenic mice demonstrate that Shh is bo th necessary and sufficient for Olg gene expression in vivo.