@article{c360dc9d98dc4a33a76c17f8eb7466a0,
title = "NPAS1 Represses the Generation of Specific Subtypes of Cortical Interneurons",
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 ofthe 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.",
author = "Amelia Stanco and Ram{\'o}n Pla and Daniel Vogt and Yiran Chen and Shyamali Mandal and Jamie Walker and Hunt, {Robert F.} and Susan Lindtner and Erdman, {Carolyn A.} and Pieper, {Andrew A.} and Hamilton, {Steven P.} and Duan Xu and Baraban, {Scott C.} and Rubenstein, {John L.R.}",
note = "Funding Information: We are grateful to S. McKnight and his lab at University of Texas Southwestern Medical Center for the generous gift of NPAS1 and NPAS3 antibodies, the NPAS1 +/− and NPAS3 +/− mice, the NPAS1 ISH construct (J. Walker), and the CMV-ARNT and CMV-NPAS1 mammalian expression vectors (L. Wu). We acknowledge the Autism Genetic Resource Exchange (AGRE) and Simons Foundation Autism Research Initiative (SFARI) for ASD genomic DNA samples, and SFARI as well for phenotypic data made available on SFARI Base. We also wish to thank all the families who donated samples, and the principal investigators involved in their collection (A. Beaudet, R. Bernier, J. Constantino, E. Cook, E. Fombonne, D. Geschwind, D. Grice, A. Klin, D. Ledbetter, C. Lord, C. Martin, D. Martin, R. Maxim, J. Miles, O. Ousley, B. Peterson, J. Piggot, C. Saulnier, M. State, W. Stone, J. Sutcliffe, C. Walsh, and E. Wijsman). Approved researchers can obtain the Simons Simplex Collection (SSC) population data set by applying at https://base.sfari.org . This work was supported by research grants to J.L.R.R. (Simons Foundation, Nina Ireland, Althea Foundation, NIMH R37 MH049428, Weston Havens Foundation), to A.S. (NIMHT32 MH089920), to S.C.B. (R01NS071785), to R.F.H. (F32NS077747), to D.X. (R01EB009756), to S.P.H. (Jaffe Family Foundation), and to A.A.P. and Steven L. McKnight (NIMH 5-RO1-MH087986). This work was also funded in part by an unrestricted endowment provided to Steven L. McKnight by an anonymous donor, used as support for J.W. ",
year = "2014",
month = dec,
day = "3",
doi = "10.1016/j.neuron.2014.10.040",
language = "English (US)",
volume = "84",
pages = "940--953",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",
}