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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


  • Harwell CC
  • Parker PR
  • Gee SM
  • Okada A
  • McConnell SK
  • Kreitzer AC
  • Kriegstein AR



Publication Data

March 22, 2012

Associated Grants

  • Agency: PHS HHS, Id: 2R37N5035710
  • Agency: NINDS NIH HHS, Id: 5P01NS048120
  • Agency: NINDS NIH HHS, Id: R01 NS035710
  • Agency: NINDS NIH HHS, Id: R01 NS035710-13

Mesh Terms

  • 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