NPAS1 Represses the Generation of Specific Subtypes of Cortical Interneurons

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2014 Dec 4

PMID 25467980

Citations 40

Authors

Amelia Stanco

Ramon Pla

Daniel Vogt

Yiran Chen

Shyamali Mandal

Jamie Walker

Robert F Hunt

Susan Lindtner

Carolyn A Erdman

Andrew A Pieper

Steven P Hamilton

Duan Xu

Scott C Baraban

John L R Rubenstein

Affiliations

Soon will be listed here.

Abstract

Little is known about genetic mechanisms that regulate the ratio of cortical excitatory and inhibitory neurons. We show that NPAS1 and NPAS3 transcription factors (TFs) are expressed in progenitor domains of the mouse basal ganglia (subpallium, MGE, and CGE). NPAS1(-/-) mutants had increased proliferation, ERK signaling, and expression of Arx in the MGE and CGE. NPAS1(-/-) mutants also had increased neocortical inhibition (sIPSC and mIPSC) and generated an excess of somatostatin(+) (SST) (MGE-derived) and vasoactive intestinal polypeptide(+) (VIP) (CGE-derived) neocortical interneurons, but had a normal density of parvalbumin(+) (PV) (MGE-derived) interneurons. In contrast, NPAS3(-/-) mutants showed decreased proliferation and ERK signaling in progenitors of the ganglionic eminences and had fewer SST(+) and VIP(+) interneurons. NPAS1 repressed activity of an Arx enhancer, and Arx overexpression resulted in increased proliferation of CGE progenitors. These results provide insights into genetic regulation of cortical interneuron numbers and cortical inhibitory tone.

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