Sonic Hedgehog Dependent Neuron-Astrocyte Crosstalk During Cortical Circuit Assembly

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.