Sonic hedgehog expression in corticofugal projection neurons directs cortical microcircuit formation.
VIDEO 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.
Pubmed ID: 22445340 RIS Download
Age Factors | Animals | Animals, Newborn | Cerebral Cortex | Corpus Callosum | DNA-Binding Proteins | Dendritic Spines | Electric Stimulation | Electroporation | Fluorobenzenes | Functional Laterality | Furans | Gene Expression Regulation, Developmental | Hedgehog Proteins | Immunoglobulin G | In Vitro Techniques | Luminescent Proteins | Matrix Attachment Region Binding Proteins | Membrane Potentials | Mice | Mice, Transgenic | Mutation | Nerve Net | Neurons | Nuclear Proteins | Patch-Clamp Techniques | Phosphopyruvate Hydratase | Pyramidal Tracts | RNA, Small Interfering | Receptors, Cell Surface | Repressor Proteins | Rhodopsin | Silver Staining | Stilbamidines | Synapses | Synaptophysin | Transcription Factors | Tumor Suppressor Proteins | gamma-Aminobutyric Acid