Lhx1 Controls Terminal Differentiation and Circadian Function of the Suprachiasmatic Nucleus

Joseph L. Bedont; Tara A. LeGates; Emily A. Slat; Mardi S. Byerly; Hong Wang; Jianfei Hu; Alan C. Rupp; Jiang Qian; G. William Wong; Erik D. Herzog; Samer Hattar; Seth Blackshaw

doi:10.1016/j.celrep.2014.03.060

Cell Reports (May 2014)

Lhx1 Controls Terminal Differentiation and Circadian Function of the Suprachiasmatic Nucleus

Joseph L. Bedont,
Tara A. LeGates,
Emily A. Slat,
Mardi S. Byerly,
Hong Wang,
Jianfei Hu,
Alan C. Rupp,
Jiang Qian,
G. William Wong,
Erik D. Herzog,
Samer Hattar,
Seth Blackshaw

Affiliations

Joseph L. Bedont: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Tara A. LeGates: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
Emily A. Slat: Department of Biology, Washington University, St. Louis, MO 63130, USA
Mardi S. Byerly: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Hong Wang: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Jianfei Hu: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Alan C. Rupp: Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
Jiang Qian: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
G. William Wong: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Erik D. Herzog: Department of Biology, Washington University, St. Louis, MO 63130, USA
Samer Hattar: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Seth Blackshaw: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

DOI: https://doi.org/10.1016/j.celrep.2014.03.060
Journal volume & issue: Vol. 7, no. 3
pp. 609 – 622

Abstract

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Vertebrate circadian rhythms are organized by the hypothalamic suprachiasmatic nucleus (SCN). Despite its physiological importance, SCN development is poorly understood. Here, we show that Lim homeodomain transcription factor 1 (Lhx1) is essential for terminal differentiation and function of the SCN. Deletion of Lhx1 in the developing SCN results in loss of SCN-enriched neuropeptides involved in synchronization and coupling to downstream oscillators, among other aspects of circadian function. Intact, albeit damped, clock gene expression rhythms persist in Lhx1-deficient SCN; however, circadian activity rhythms are highly disorganized and susceptible to surprising changes in period, phase, and consolidation following neuropeptide infusion. Our results identify a factor required for SCN terminal differentiation. In addition, our in vivo study of combinatorial SCN neuropeptide disruption uncovered synergies among SCN-enriched neuropeptides in regulating normal circadian function. These animals provide a platform for studying the central oscillator’s role in physiology and cognition.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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