Neuropsin (OPN5) Mediates Local Light-Dependent Circadian Responses in Murine Skin

Abstract

Nearly all mammalian tissues have functional, autonomous circadian clocks, which free-run with non-24-hour periods and must be synchronized (entrained) to the 24-hour 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. A population of LEF1-positive stem cells in hair and vibrissal follicles 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 on Opn5 function. In Opn4^-/-; Pde6b^rd1/rd1 mice that cannot behaviorally entrain to light-dark cycles, skin clock gene cycling remains phase-entrained 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 for murine skin, similar to pathways previously described for invertebrates and certain non-mammalian vertebrates.

Keywords: circadian rhythms, opsin, opn5, neuropsin, entrainment, skin