title: Regulation of photoreceptor Per1 and Per2 by light, dopamine and a circadian clock.
abstract: In the Xenopus laevis retina, a principal model for retinal circadian organization, photoreceptors have all the properties of circadian oscillators. However, rhythmic oscillations of Per1 gene expression in the inner retina (but not photoreceptors) have been reported in mice with the suggestion that mice and frogs have a different retinal circadian organization. Although it is known that two period genes (xPer1 and xPer2) exhibit different temporal patterns of expression in the Xenopus retina, and that one (xPer2) is directly responsive to light and dopamine, it is not known whether this reflects the properties of period genes within photoreceptor oscillators or among distinct retinal cell populations. We addressed this by determining the cellular site of light and dopamine regulated xPer2 expression, and the diurnal expression of both xPer1 and xPer2 using in situ hybridization. Our data show that both xPer1 and xPer2 are expressed in most cell types in the retina, including inner nuclear neurons and ganglion cells. However, light and quinpirole, a dopamine agonist, increase xPer2 levels specifically in photoreceptors, and the effect of quinpirole, but not light, is blocked by pCPT-cAMP. Furthermore, antiphasic diurnal expression of xPer1 and xPer2 also occurs in photoreceptors. Our analysis does not provide insight into the near constitutive expression of period genes in the inner retina, but supports a model in which light- and dopamine regulated-xPer2 and rhythmic xPer1 play critical roles in entrainment and circadian oscillations within photoreceptors.
authors.affiliation: Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. jbeshars@mcw.edu
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Besharse
authors.forename: Minhong
authors.initials: M
authors.lastname: Zhuang
authors.forename: Katie
authors.initials: K
authors.lastname: Freeman
authors.forename: Joseph
authors.initials: J
authors.lastname: Fogerty
mesh_terms: D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D002452:Cell Count / Q000379:methods; D002940:Circadian Rhythm / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005123:Eye; D005136:Eye Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D056950:Period Circadian Proteins; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000528:radiation effects; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology; D029867:Xenopus Proteins; D014982:Xenopus laevis
chemical_list: D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D005136:Eye Proteins; C539025:Per1 protein, Xenopus; C539023:Per1 protein, mouse; C498845:Per2 protein, Xenopus; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D013873:Thionucleotides; D029867:Xenopus Proteins; D019257:Quinpirole; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D000242:Cyclic AMP; D004298:Dopamine