Abstract
Purpose: :
Many aspects of biochemical, cellular, developmental and physiological processes display robust daily changes in the vertebrate retina. Yet a little is known about where the retinal circadian clock is located in the distinctly stratified retinal cell layers and how it controls the retinal circadian rhythms. Here the zebrafish (Danio rerio) is used to elucidate molecular genetic mechanisms that underlie the retinal circadian rhythmicity.
Methods: :
In situ hybridization, genetic analysis and fluorescence microscopy.
Results: :
In situ hybridization analysis shows zebrafish clock1a, cryptochrome1a and period1a are rhythmically expressed in photoreceptor cells and ganglion cells: period1a peaks early morning (ZT4), whereas clock1a and cryptochrome1a peaks late evening (ZT12). Light appears to enhance clock1a and cryptochrome1a retinal expression but to repress period1a. Retinal expression of clock1a, cryptochrome1a and period1a is completely abolished in the zebrafish carrying a missense mutation in axin1 (mbl), encoding a scaffolding protein in the Wnt signaling pathway. In addition, normal retinal oscillations of clock1a, cryptochrome1a and period1a are all altered in melatonin–treated zebrafish.
Conclusions: :
Taken together, these results support the notion that the photoreceptor circadian clock, coupled with neuromodulators such as melatonin, may regulate the retinal circadian rhythmicity.
Keywords: circadian rhythms • photoreceptors • gene/expression