Abstract
BackgroundAlthough an endogenous circadian clock located in the retinal photoreceptor layer governs various physiological events including melatonin rhythms in Xenopus laevis, it remains unknown which of the photoreceptors, rod and/or cone, is responsible for the circadian regulation of melatonin release.Methodology/Principal FindingsWe selectively disrupted circadian clock function in either the rod or cone photoreceptor cells by generating transgenic Xenopus tadpoles expressing a dominant-negative CLOCK (XCLΔQ) under the control of a rod or cone-specific promoter. Eyecup culture and continuous melatonin measurement revealed that circadian rhythms of melatonin release were abolished in a majority of the rod-specific XCLΔQ transgenic tadpoles, although the percentage of arrhythmia was lower than that of transgenic tadpole eyes expressing XCLΔQ in both rods and cones. In contrast, whereas a higher percentage of arrhythmia was observed in the eyes of the cone-specific XCLΔQ transgenic tadpoles compare to wild-type counterparts, the rate was significantly lower than in rod-specific transgenics. The levels of the transgene expression were comparable between these two different types of transgenics. In addition, the average overall melatonin levels were not changed in the arrhythmic eyes, suggesting that CLOCK does not affect absolute levels of melatonin, only its temporal expression pattern.Conclusions/SignificanceThese results suggest that although the Xenopus retina is made up of approximately equal numbers of rods and cones, the circadian clocks in the rod cells play a dominant role in driving circadian melatonin rhythmicity in the Xenopus retina, although some contribution of the clock in cone cells cannot be excluded.
Highlights
Vertebrate circadian clocks are distributed in a wide variety of tissues, where they generate local rhythms in many critical pathways that are fundamental for the proper physiology of each tissue
We have previously reported that overexpression of a dominant negative Xenopus CLOCK (XCLDQ; lacking the transactivation domain of normal CLOCK) in all retinal photoreceptors in Xenopus resulted in abolishment of the circadian melatonin rhythmicity [15]
To further investigate how each of the two retinal photoreceptor cell types in Xenopus contributes to the circadian rhythmicity, we generated groups of transgenic animals expressing XCLDQ driven by one of two different promoters: the rod opsin promoter
Summary
Vertebrate circadian clocks are distributed in a wide variety of tissues, where they generate local rhythms in many critical pathways that are fundamental for the proper physiology of each tissue Lesioning studies of the retina demonstrated that isolated photoreceptor layers (containing rods and cones) were capable of producing melatonin rhythms without contribution from other retinal cell types. These types of lesioning studies do not rule out a potential role of clocks in other cell types within the intact retina. To address this issue more directly, previous work in our lab used a transgenic approach to genetically ablate the clock in the intact retina. An endogenous circadian clock located in the retinal photoreceptor layer governs various physiological events including melatonin rhythms in Xenopus laevis, it remains unknown which of the photoreceptors, rod and/or cone, is responsible for the circadian regulation of melatonin release
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