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Neuron DOI:10.1016/j.neuron.2012.02.009

Sonic hedgehog expression in corticofugal projection neurons directs cortical microcircuit formation.

Publication TypeJournal Article
Year of Publication2012
AuthorsHarwell, CC, Parker, PRL, Gee, SM, Okada, A, McConnell, SK, Kreitzer, AC, Kriegstein, AR
Date Published2012 Mar 22
KeywordsAge Factors, Animals, Animals, Newborn, Cerebral Cortex, Corpus Callosum, Dendritic Spines, DNA-Binding Proteins, Electric Stimulation, Electroporation, Fluorobenzenes, Functional Laterality, Furans, gamma-Aminobutyric Acid, 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, Receptors, Cell Surface, Repressor Proteins, Rhodopsin, RNA, Small Interfering, Silver Staining, Stilbamidines, Synapses, Synaptophysin, Transcription Factors, Tumor Suppressor Proteins

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.


Alternate JournalNeuron
PubMed ID22445340
PubMed Central IDPMC3551478
Grant ListR01 NS035710 / NS / NINDS NIH HHS / United States
P01 NS048120 / NS / NINDS NIH HHS / United States
2R37N5035710 / / PHS HHS / United States
5P01NS048120 / NS / NINDS NIH HHS / United States
R01 NS035710-13 / NS / NINDS NIH HHS / United States