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Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical synapse development
Yajun Xie1, Aaron T Kuan1, Wengang Wang2
1Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Cell Reports
|February 23, 2022
Summary
Sonic hedgehog (Shh) pathway signaling in astrocytes coordinates brain circuit assembly. Shh from neurons shapes astrocyte identity and promotes synapse formation, crucial for neural development.
Area of Science:
- Neuroscience
- Developmental Biology
- Astrocyte Biology
Background:
- Neuron-glia interactions are essential for synapse formation and neural circuit assembly.
- Astrocyte molecular identity and function are critical for proper brain development.
Purpose of the Study:
- To investigate the role of Sonic hedgehog (Shh) pathway signaling in cortical astrocytes.
- To determine how Shh signaling influences astrocyte molecular identity and synaptic connectivity.
- To elucidate the contribution of Shh-dependent genes to astrocyte morphology and synapse formation.
Main Methods:
- Analysis of Shh receptor (Ptch1) expression in developing cortical astrocytes.
- Genetic manipulation to alter Shh signaling in cortical neurons and astrocytes.
- Assessment of astrocyte complexity, coverage, and synapse formation.
- Gene expression analysis of Shh-dependent targets (Lrig1, Sparc).
Main Results:
- Shh signaling in cortical astrocytes is necessary and sufficient for regulating synaptic development and astrocyte identity.
- Loss of Shh in layer V neurons impairs astrocyte complexity and synaptic coverage.
- Activation of Shh signaling in astrocytes promotes excitatory synapse formation.
- Shh-dependent genes Lrig1 and Sparc differentially impact astrocyte morphology and synapse formation.
Conclusions:
- Sonic hedgehog (Shh) secreted by deep-layer cortical neurons specializes astrocytes during development.
- This Shh-mediated specialization shapes astrocyte molecular and functional features, influencing circuit assembly and function.
- Astrocyte-neuron communication via the Shh pathway is critical for establishing precise synaptic connectivity.
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