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Curr Biol. 2019 Oct 21;29(20):3478-3487.e4. doi: 10.1016/j.cub.2019.08.063. Epub 2019 Oct 10.

Neuropsin (OPN5) Mediates Local Light-Dependent Induction of Circadian Clock Genes and Circadian Photoentrainment in Exposed Murine Skin.

Author information

1
Department of Ophthalmology, Campus Box 358058, University of Washington School of Medicine, 750 Republican St., Seattle, WA 98109, USA. Electronic address: buhre@uw.edu.
2
Center for Chronobiology, University of Cincinnati, College of Medicine, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA; The Visual Systems Group, Abrahamson Pediatric Eye Institute, University of Cincinnati, College of Medicine, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA; Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, College of Medicine, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA.
3
Department of Ophthalmology, Campus Box 358058, University of Washington School of Medicine, 750 Republican St., Seattle, WA 98109, USA.
4
Center for Chronobiology, University of Cincinnati, College of Medicine, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA; The Visual Systems Group, Abrahamson Pediatric Eye Institute, University of Cincinnati, College of Medicine, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA; Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, College of Medicine, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA; Department of Ophthalmology, University of Cincinnati, College of Medicine, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA. Electronic address: richard.lang@cchmc.org.
5
Department of Ophthalmology, Campus Box 358058, University of Washington School of Medicine, 750 Republican St., Seattle, WA 98109, USA; Department of Biological Structure and Department of Pathology, University of Washington School of Medicine, 750 Republican St., Seattle, WA 98109, USA.

Abstract

Nearly all mammalian tissues have functional, autonomous circadian clocks, which free-run with non-24 h periods and must be synchronized (entrained) to the 24 h day. This entrainment mechanism is thought to be hierarchical, with photic input to the retina entraining the master circadian clock in the suprachiasmatic nuclei (SCN) and the SCN in turn synchronizing peripheral tissues via endocrine mechanisms. Here, we assess the function of a population of melanocyte precursor cells in hair and vibrissal follicles that express the photopigment neuropsin (OPN5). Organotypic cultures of murine outer ear and vibrissal skin entrain to a light-dark cycle ex vivo, requiring cis-retinal chromophore and Opn5 gene function. Short-wavelength light strongly phase shifts skin circadian rhythms ex vivo via an Opn5-dependent mechanism. In vivo, the normal amplitude of Period mRNA expression in outer ear skin is dependent on both the light-dark cycle and Opn5 function. In Opn4-/-; Pde6brd1/rd1 mice that cannot behaviorally entrain to light-dark cycles, the phase of skin-clock gene expression remains synchronized to the light-dark cycle, even as other peripheral clocks remain phase-locked to the free-running behavioral rhythm. Taken together, these results demonstrate the presence of a direct photic circadian entrainment pathway and direct light-response elements for clock genes in murine skin, similar to pathways previously described for invertebrates and certain non-mammalian vertebrates.

KEYWORDS:

circadian rhythms; entrainment; neuropsin; opn5; opsin; skin

PMID:
31607531
PMCID:
PMC6814305
[Available on 2020-10-21]
DOI:
10.1016/j.cub.2019.08.063

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