Molecular control of Xenopus retinal circadian rhythms.

Abstract

Vertebrate retinas contain endogenous circadian clocks that control many aspects of retinal physiology. Our work has focused on studying the molecular mechanism of this clock and the way in which it controls the many cellular rhythms within the retina. These studies focus on the retina of Xenopus laevis, a well-established model system extensively used for the study of both retinal physiology and circadian function. We have cloned Xenopus homologues of the genes thought to be critical for vertebrate clock function, including Clock, Bmal1, cryptochromes and period, as well as other rhythmic genes such as nocturnin. We have used these genes to manipulate the clock within different subsets of retinal photoreceptors via cell-specific promoters, in order to study the location of the clock within the retina. These in vivo experiments have shown that photoreceptor cells contain clocks that are necessary for the rhythmic production of melatonin. We have also used biochemical approaches to further investigate the molecular events that drive specific rhythmic outputs, such as circadian regulation of nocturnin gene transcription and control of post-transcriptional events within these clock-containing cells.