Sonic hedgehog expression in corticofugal projection neurons directs cortical microcircuit formation |
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Authors: | Harwell Corey C Parker Philip R L Gee Steven M Okada Ami McConnell Susan K Kreitzer Anatol C Kriegstein Arnold R |
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Affiliation: | Eli and Edythe Broad Institute of Regeneration Medicine and Stem Cell Research, University of California-San Francisco, San Francisco, CA 94143, USA. harwellc@stemcell.ucsf.edu |
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Abstract: | The precise connectivity of inputs and outputs is critical for cerebral cortex function; however, the cellular mechanisms that establish these connections are poorly understood. Here, we show that the secreted molecule Sonic Hedgehog (Shh) is involved in synapse formation of a specific cortical circuit. Shh is expressed in layer V corticofugal projection neurons and the Shh receptor, Brother of CDO (Boc), is expressed in local and callosal projection neurons of layer II/III that synapse onto the subcortical projection neurons. Layer V neurons of mice lacking functional Shh exhibit decreased synapses. Conversely, the loss of functional Boc leads to a reduction in the strength of synaptic connections onto layer Vb, but not layer II/III, pyramidal neurons. These results demonstrate that Shh is expressed in postsynaptic target cells while Boc is expressed in a complementary population of presynaptic input neurons, and they function to guide the formation of cortical microcircuitry. VIDEO ABSTRACT: |
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