Sonic hedgehog signaling in astrocytes
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Cellular and Molecular Life Sciences
REVIEW
Sonic hedgehog signaling in astrocytes Steven A. Hill1 · Marissa Fu1 · A. Denise R. Garcia1,2 Received: 17 April 2020 / Revised: 2 September 2020 / Accepted: 5 October 2020 © The Author(s) 2020
Abstract Astrocytes are complex cells that perform a broad array of essential functions in the healthy and injured nervous system. The recognition that these cells are integral components of various processes, including synapse formation, modulation of synaptic activity, and response to injury, underscores the need to identify the molecular signaling programs orchestrating these diverse functional properties. Emerging studies have identified the Sonic hedgehog (Shh) signaling pathway as an essential regulator of the molecular identity and functional properties of astrocytes. Well established as a powerful regulator of diverse neurodevelopmental processes in the embryonic nervous system, its functional significance in astrocytes is only beginning to be revealed. Notably, Shh signaling is active only in discrete subpopulations of astrocytes distributed throughout the brain, a feature that has potential to yield novel insights into functional specialization of astrocytes. Here, we discuss Shh signaling and emerging data that point to essential roles for this pleiotropic signaling pathway in regulating various functional properties of astrocytes in the healthy and injured brain. Keywords Astrocyte · Sonic hedgehog · Gli1 · Glia · Neuron-astrocyte communication
Introduction Astrocytes are the most abundant glial cells in the brain and are vital for normal brain function. Astrocytes are no longer relegated to the sidelines as monolithic “support cells”, and crosstalk between astrocytes and neurons is now known to be required for a number of important processes [1]. Astrocytes are required for synapses to form between neurons, and a number of studies have identified astrocyte-derived molecules that are required for the formation and function of individual synapses [2]. These include both astrocyte-secreted molecules, such as SPARC, hevin, thrombospondins, and chordin-like 1, whose presence regulates the insertion of specific receptors into developing synapses, and direct astrocyte–neuron contact via neuroligin/neurexin linkages, which also regulates astrocyte morphogenesis [3–7]. In addition to their roles in synapse formation and maturation, astrocytes * A. Denise R. Garcia [email protected] 1
Department of Biology, Drexel University, Philadelphia, PA 19104, USA
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA
2
are also vital for neuronal circuit function through their regulation of the extracellular ionic environment. Disruptions in astrocytic proteins, such as the inward rectifying potassium channel Kir4.1, produce circuit abnormalities throughout the CNS, including in the lateral habenula, striatum, and spinal cord, which are implicated in neurological diseases, such as depression, Huntington’s disease, and amy
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