A subpopulation of astrocyte progenitors defined by Sonic hedgehog signaling

ABSTRACT The molecular signaling pathway, Sonic hedgehog (Shh), is critical for the proper development of the central nervous system. The requirement for Shh signaling in neuronal and oligodendrocyte development in the developing embryo are well established. Here, we show that Shh signaling also operates in a subpopulation of progenitor cells that generate cortical astrocytes. In the neonatal brain, cells expressing the Shh target gene, Gli1 , are found in the subventricular zone (SVZ), a germinal zone harboring astrocyte progenitor cells. Using a genetic inducible fate mapping strategy, we show that these cells give rise to half of the cortical astrocyte population, suggesting that the cortex harbors astrocytes from different lineages. Shh activity in SVZ progenitor cells is transient but recurs in a subpopulation of mature astrocytes localized in layers IV and V in a manner independent of their lineage. These data identify a novel role for Shh signaling in cortical astrocyte development and support a growing body of evidence pointing to astrocyte heterogeneity.