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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Video-Audio Media
MeSH terms
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Age Factors
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Animals
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Animals, Newborn
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Cerebral Cortex / cytology*
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Cerebral Cortex / growth & development
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Channelrhodopsins
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Corpus Callosum / cytology
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Corpus Callosum / growth & development
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DNA-Binding Proteins / metabolism
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Dendritic Spines / metabolism
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Dendritic Spines / physiology
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Electric Stimulation
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Electroporation / methods
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Fluorobenzenes / metabolism
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Functional Laterality / genetics
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Furans / metabolism
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Gene Expression Regulation, Developmental / genetics
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Gene Expression Regulation, Developmental / physiology*
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Hedgehog Proteins / genetics
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Hedgehog Proteins / metabolism*
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Immunoglobulin G / genetics
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Immunoglobulin G / metabolism
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In Vitro Techniques
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Matrix Attachment Region Binding Proteins / metabolism
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Membrane Potentials / genetics
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Mice
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Mice, Transgenic
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Mutation / genetics
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Nerve Net / cytology
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Nerve Net / metabolism*
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Neurons / metabolism*
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Neurons / ultrastructure
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Nuclear Proteins / metabolism
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Patch-Clamp Techniques
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Phosphopyruvate Hydratase / metabolism
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Pyramidal Tracts / physiology*
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Repressor Proteins / metabolism
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Silver Staining / methods
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Stilbamidines / metabolism
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Synapses / metabolism
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Synapses / ultrastructure
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Synaptophysin / genetics
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Synaptophysin / metabolism
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Transcription Factors / metabolism
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Tumor Suppressor Proteins / metabolism
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Ubiquitin-Protein Ligases
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gamma-Aminobutyric Acid / metabolism
Substances
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2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
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3,4-difluorobenzyloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)-(5H)-furan-2-one
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Bcl11b protein, mouse
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Boc protein, mouse
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Channelrhodopsins
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DNA-Binding Proteins
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Fluorobenzenes
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Furans
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Hedgehog Proteins
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Immunoglobulin G
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Luminescent Proteins
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Matrix Attachment Region Binding Proteins
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Nuclear Proteins
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RNA, Small Interfering
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Receptors, Cell Surface
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Repressor Proteins
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SATB2 protein, mouse
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Shh protein, mouse
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Stilbamidines
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Synaptophysin
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Transcription Factors
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Tumor Suppressor Proteins
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gamma-Aminobutyric Acid
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Trim27 protein, mouse
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Ubiquitin-Protein Ligases
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Phosphopyruvate Hydratase