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

Nat Neurosci
Authors
Keywords
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.

Year of Publication
2014
Journal
Nat Neurosci
Volume
17
Issue
8
Pages
1046-54
Date Published
2014 Aug
ISSN
1546-1726
URL
DOI
10.1038/nn.3757
PubMed ID
24997765
PubMed Central ID
PMC4188416
Links
Grant list
R01 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
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