Neuron
Volume 73, Issue 6, 22 March 2012, Pages 1116-1126
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Article
Sonic Hedgehog Expression in Corticofugal Projection Neurons Directs Cortical Microcircuit Formation

https://doi.org/10.1016/j.neuron.2012.02.009Get rights and content
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Summary

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.

Highlights

► Sonic Hedgehog is expressed in subcortical projection neurons in the neocortex ► Cortical loss of Sonic Hedgehog leads to decreased synapses in layer V neurons ► Boc is expressed in callosal projection neurons and is not required for axon guidance ► Sonic Hedgehog and its receptor Boc function in the assembly of cortical circuits.

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