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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)609-622
Number of pages14
JournalCell Reports
Volume7
Issue number3
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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