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Elife. 2014 Jul 17;3:e03357. doi: 10.7554/eLife.03357.

Lhx1 maintains synchrony among circadian oscillator neurons of the SCN.

Author information

1
Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States mhatori@a6.keio.jp.
2
Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
3
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
4
Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States panda@salk.edu.

Abstract

The robustness and limited plasticity of the master circadian clock in the suprachiasmatic nucleus (SCN) is attributed to strong intercellular communication among its constituent neurons. However, factors that specify this characteristic feature of the SCN are unknown. Here, we identified Lhx1 as a regulator of SCN coupling. A phase-shifting light pulse causes acute reduction in Lhx1 expression and of its target genes that participate in SCN coupling. Mice lacking Lhx1 in the SCN have intact circadian oscillators, but reduced levels of coupling factors. Consequently, the mice rapidly phase shift under a jet lag paradigm and their behavior rhythms gradually deteriorate under constant condition. Ex vivo recordings of the SCN from these mice showed rapid desynchronization of unit oscillators. Therefore, by regulating expression of genes mediating intercellular communication, Lhx1 imparts synchrony among SCN neurons and ensures consolidated rhythms of activity and rest that is resistant to photic noise.

KEYWORDS:

Lhx1; Ror-alpha; VIP; circadian rhythm; suprachiasmatic nucleus

Comment in

PMID:
25035422
PMCID:
PMC4137275
DOI:
10.7554/eLife.03357
[Indexed for MEDLINE]
Free PMC Article

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