Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical synapse development.
Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical synapse development.
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星形胶质细胞-神经元串扰通过刺猬信号介导皮质突触发育。
DOI:
10.1016/j.celrep.2022.110416
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发表时间:
2022-02-22
期刊:
影响因子:
8.8
通讯作者:
Harwell CC
中科院分区:
文献类型:
--
作者:
Xie Y;Kuan AT;Wang W;Herbert ZT;Mosto O;Olukoya O;Adam M;Vu S;Kim M;Tran D;Gómez N;Charpentier C;Sorour I;Lacey TE;Tolstorukov MY;Sabatini BL;Lee WA;Harwell CC
Neuron-glia interactions play a critical role in the regulation of synapse formation and circuit assembly. Here we demonstrate that canonical Sonic hedgehog (Shh) pathway signaling in cortical astrocytes acts to coordinate layer-specific synaptic connectivity. We show that the Shh receptor Ptch1 is expressed by cortical astrocytes during development and that Shh signaling is necessary and sufficient to promote the expression of genes involved in regulating synaptic development and layer-enriched astrocyte molecular identity. Loss of Shh in layer V neurons reduces astrocyte complexity and coverage by astrocytic processes in tripartite synapses; conversely, cell-autonomous activation of Shh signaling in astrocytes promotes cortical excitatory synapse formation. Furthermore, Shh-dependent genes Lrig1 and Sparc distinctively contribute to astrocyte morphology and synapse formation. Together, these results suggest that Shh secreted from deep-layer cortical neurons acts to specialize the molecular and functional features of astrocytes during development to shape circuit assembly and function. Xie et al. show that Sonic hedgehog expressed by cortical layer V neurons signals to Ptch1-expressing astrocytes where it is necessary to promote the expression of layer-enriched astrocyte gene networks that control synapse formation and astrocyte morphological complexity.
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