Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Cell Rep. 2022 Feb 22;38(8):110416. doi: 10.1016/j.celrep.2022.110416.
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.
神经元-胶质细胞相互作用在调节突触形成和回路组装中起着关键作用。在这里，我们证明了皮层星形胶质细胞中经典 Sonic hedgehog (Shh) 信号通路的信号作用是协调特定层的突触连接。我们表明，Shh 受体 Ptch1 在发育过程中由皮层星形胶质细胞表达，Shh 信号是促进参与调节突触发育和富含层的星形胶质细胞分子特征的基因表达所必需和充分的。在 V 层神经元中缺失 Shh 会减少三突触中星形胶质细胞突起的复杂性和覆盖范围；相反，星形胶质细胞中 Shh 信号的细胞自主激活促进了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，从深层皮层神经元分泌的 Shh 作用是在发育过程中专门化星形胶质细胞的分子和功能特征，以形成回路组装和功能。
