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Nat Neurosci DOI:10.1038/nn.3757

Gene co-regulation by Fezf2 selects neurotransmitter identity and connectivity of corticospinal neurons.

Publication TypeJournal Article
Year of Publication2014
AuthorsLodato, S, Molyneaux, BJ, Zuccaro, E, Goff, LA, Chen, H-H, Yuan, W, Meleski, A, Takahashi, E, Mahony, S, Rinn, JL, Gifford, DK, Arlotta, P
JournalNat Neurosci
Volume17
Issue8
Pages1046-54
Date Published2014 Aug
ISSN1546-1726
KeywordsAnimals, DNA-Binding Proteins, Gene Expression Regulation, Genes, Suppressor, Mice, Mice, Knockout, Mice, Transgenic, Motor Neurons, Nerve Tissue Proteins, Neurotransmitter Agents, Promoter Regions, Genetic, Pyramidal Tracts, Signal Transduction
Abstract

The neocortex contains an unparalleled diversity of neuronal subtypes, each defined by distinct traits that are developmentally acquired under the control of subtype-specific and pan-neuronal genes. The regulatory logic that orchestrates the expression of these unique combinations of genes is unknown for any class of cortical neuron. Here, we report that Fezf2 is a selector gene able to regulate the expression of gene sets that collectively define mouse corticospinal motor neurons (CSMN). We find that Fezf2 directly induces the glutamatergic identity of CSMN via activation of Vglut1 (Slc17a7) and inhibits a GABAergic fate by repressing transcription of Gad1. In addition, we identify the axon guidance receptor EphB1 as a target of Fezf2 necessary to execute the ipsilateral extension of the corticospinal tract. Our data indicate that co-regulated expression of neuron subtype-specific and pan-neuronal gene batteries by a single transcription factor is one component of the regulatory logic responsible for the establishment of CSMN identity.

URLhttp://dx.doi.org/10.1038/nn.3757
DOI10.1038/nn.3757
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24997765?dopt=Abstract

Alternate JournalNat. Neurosci.
PubMed ID24997765
PubMed Central IDPMC4188416
Grant ListR01 NS078097 / NS / NINDS NIH HHS / United States
R01 NS062849 / NS / NINDS NIH HHS / United States
R01 NS078164 / NS / NINDS NIH HHS / United States
HD069001 / HD / NICHD NIH HHS / United States
R01 MH101268 / MH / NIMH NIH HHS / United States
MH101268 / MH / NIMH NIH HHS / United States
R21 HD069001 / HD / NICHD NIH HHS / United States
HD078561 / HD / NICHD NIH HHS / United States
NS062849 / NS / NINDS NIH HHS / United States
NS078164 / NS / NINDS NIH HHS / United States
R01 HD078561 / HD / NICHD NIH HHS / United States