Sonic Hedgehog Dependent Neuron-Astrocyte Crosstalk During Cortical Circuit Assembly

项目概要 神经元-胶质细胞关系在突触形成和神经元的调节中起着关键作用 规格。神经元和星形胶质细胞沟通和交流的细胞和分子机制 坐标不太理解。本提案中的实验将揭示分子和细胞 神经元衍生的 SHH 蛋白协调皮质星形胶质细胞的细胞行为的机制 促进大脑神经回路的形成和功能。在我们的研究中，我们利用了大 小鼠遗传工具的补充使我们能够特异性地操纵星形胶质细胞中的 Shh 信号传导。使用 最先进的光学和电子显微镜方法，我们将定义之间的具体相互作用 星形胶质细胞和神经元依赖于 Shh 信号传导并评估星形胶质细胞如何影响发育 的功能电路。总的来说，这些目标将为理解交付、接收提供一个框架 以及发育中皮层中细胞对 SHH 的反应。

Project Summary Neuronal-glial relationships play a critical role in the regulation of synapse formation and neuronal specification. The cellular and molecular mechanisms by which neurons and astrocytes communicate and coordinate are not well understood. The experiments in this proposal will uncover the molecular and cellular mechanisms by which neuron derived SHH protein can coordinate the cell behaviors of cortical astrocytes to facilitate the formation and function of neural circuits in the brain. In our studies we take advantage of the large complement of mouse genetic tools that allows us to specifically manipulate Shh signaling in astrocytes. Using cutting edge light and electron microscopy approaches we will define how specific interactions between astrocytes and neurons are dependent on Shh signaling and assess how astrocytes influence the development of functional circuits. Collectively these aims will provide a framework for understanding the delivery, reception and cellular response to SHH in the developing cortex.