@article{f491832c8a0744e485d21098c1e76f37,
title = "Gene co-regulation by Fezf2 selects neurotransmitter identity and connectivity of corticospinal neurons",
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.",
author = "Simona Lodato and Molyneaux, {Bradley J.} and Emanuela Zuccaro and Goff, {Loyal A.} and Chen, {Hsu Hsin} and Wen Yuan and Alyssa Meleski and Emi Takahashi and Shaun Mahony and Rinn, {John L.} and Gifford, {David K.} and Paola Arlotta",
note = "Funding Information: We would like to thank A. McMahon and J. Macklis for insightful advice in the early stages of the work; S. McConnell (Stanford University) for her generous sharing of the Fezf2{\o}PLAP line; J. Macklis (Harvard University), R. Hevner (Seattle Children{\textquoteright}s Research Institute), A. Catic (Massachusetts General Hospital) and S. Sykes (Massachusetts General Hospital) for sharing of antibodies and expression vectors; C. O{\textquoteright}Donnell and D. Cacchiarelli for discussions on ChIP-seq analysis.; Z. Trayes-Gibson, E. Stronge and A. Iannone for outstanding technical support and for reading the manuscript; and A. Goodwin for careful editing of the manuscript and comments. This work was supported by grants from the US National Institutes of Health (NS062849, MH101268, NS078164 to P.A.), (HD078561 and HD069001 to E.T.), the New York Stem Cell Foundation (Robertson Investigator award to P.A.) and the Harvard Stem Cell Institute to P.A.",
year = "2014",
month = aug,
doi = "10.1038/nn.3757",
language = "English (US)",
volume = "17",
pages = "1046--1054",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Research",
number = "8",
}