title: Lhx1 maintains synchrony among circadian oscillator neurons of the SCN.
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.
authors.affiliation: Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States mhatori@a6.keio.jp.
authors.forename: Megumi
authors.initials: M
authors.lastname: Hatori
authors.affiliation: Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Shubhroz
authors.initials: S
authors.lastname: Gill
authors.affiliation: Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Ludovic S
authors.initials: LS
authors.lastname: Mure
authors.affiliation: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Martyn
authors.initials: M
authors.lastname: Goulding
authors.affiliation: Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
authors.forename: Dennis D M
authors.initials: DD
authors.lastname: O'Leary
authors.affiliation: Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, United States panda@salk.edu.
authors.forename: Satchidananda
authors.initials: S
authors.lastname: Panda
mesh_terms: D000818:Animals; D002450:Cell Communication; D057906:Circadian Clocks / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020179:Jet Lag Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060850:LIM-Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism; D017440:Photoperiod; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D060850:LIM-Homeodomain Proteins; C499523:Lhx1 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors
keywords: Lhx1; Ror-alpha; VIP; circadian rhythm; suprachiasmatic nucleus