Abstract
BackgroundThe 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. However, Shh activity is found in discrete subpopulations of astrocytes in the postnatal and adult brain. Whether Shh signaling plays a role in astrocyte development is not well understood.MethodsHere, we use a genetic inducible fate mapping approach to mark and follow a population of glial progenitor cells expressing the Shh target gene, Gli1, in the neonatal and postnatal brain.ResultsIn the neonatal brain, Gli1-expressing cells are found in the dorsolateral corner of the subventricular zone (SVZ), a germinal zone harboring astrocyte progenitor cells. Our data show that these cells give rise to half of the cortical astrocyte population, demonstrating their substantial contribution to the cellular composition of the cortex. Further, these data suggest that the cortex harbors astrocytes from different lineages. Gli1 lineage astrocytes are distributed across all cortical layers, positioning them for broad influence over cortical circuits. Finally, we show that Shh activity recurs in mature astrocytes in a lineage-independent manner, suggesting cell-type dependent roles of the pathway in driving astrocyte development and function.ConclusionThese data identify a novel role for Shh signaling in cortical astrocyte development and support a growing body of evidence pointing to astrocyte heterogeneity.
Highlights
Astrocytes encompass a diverse population of cells that possess a broad array of functional properties that are essential for nervous system function
Astrocytes in the Gli1 lineage are broadly distributed in the cortex We first examined the expression of Gli1 in the early postnatal mouse cortex in Gli1nlacZ/+ mice carrying a nuclear lacZ in the Gli1 locus [21]
There was a further expansion observed at P7 (Fig. 1), suggesting that Gli1-expressing cells marked at postnatal day 0 (P0) correspond to actively dividing glial progenitor cells
Summary
Astrocytes encompass a diverse population of cells that possess a broad array of functional properties that are essential for nervous system function. They are responsible for neurotransmitter clearance, ion buffering, synapse formation, maintenance of the blood brain barrier, and provide energetic support for neurons [1]. The Sonic hedgehog (Shh) signaling pathway is best characterized during embryonic neurodevelopment, where it exerts powerful influence over a broad array of neurodevelopmental processes, including patterning and morphogenesis, axon pathfinding, and cell type specification of ventral motor neurons and oligodendrocytes [6]. Whether Shh signaling plays a role in astrocyte development is not well understood
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