Abstract：
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.
摘要：
神经元-神经胶质相互作用在突触形成和电路组装的调节中起关键作用。在这里，我们证明了皮质星形胶质细胞中的典型Sonichedgehog（Shh）通路信号可以协调层特异性突触连接。我们表明，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富含层的星形胶质细胞分子身份的基因表达是必要且充分的。在V层神经元中Shh的丢失降低了星形胶质细胞的复杂性和在三部分突触中星形胶质细胞过程的覆盖;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形成。此外，Shh依赖性基因Lrig1和Sparc分别有助于星形胶质细胞形态和突触形成。一起,这些结果表明，深层皮质神经元分泌的Shh可以在发育过程中专门研究星形胶质细胞的分子和功能特征，以形成电路组装和功能。
