Neuropsin (OPN5) Mediates Local Light-Dependent Induction of Circadian Clock Genes and Circadian Photoentrainment in Exposed 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. 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 on Opn5 function. In Opn4 −/− ; Pde6b rd1/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.