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
Harwell CC
中科院分区:
生物学1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

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神经元-胶质细胞相互作用在突触形成和电路组装的调节中发挥着关键作用。在这里,我们证明了皮质星形胶质细胞中典型的 Sonic Hedgehog (Shh) 通路信号传导可协调层特异性突触连接。我们发现,Shh 受体 Ptch1 在发育过程中由皮质星形胶质细胞表达,并且 Shh 信号传导对于促进参与调节突触发育和层丰富星形胶质细胞分子身份的基因的表达是必要且充分的。 V 层神经元中 Shh 的缺失会降低星形胶质细胞的复杂性和三方突触中星形胶质细胞过程的覆盖范围;相反,星形胶质细胞中Shh信号的细胞自主激活促进皮质兴奋性突触的形成。此外,Shh 依赖性基因 Lrig1 和 Sparc 对星形胶质细胞形态和突触形成有独特的贡献。总之,这些结果表明,深层皮质神经元分泌的Shh在星形胶质细胞发育过程中发挥着专门化分子和功能特征的作用,以塑造电路组装和功能。谢等人。研究表明,皮层 V 层神经元表达的 Sonic Hedgehog 信号向表达 Ptch1 的星形胶质细胞发出信号,需要促进控制突触形成和星形胶质细胞形态复杂性的层丰富星形胶质细胞基因网络的表达。
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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