RT Journal Article
SR Electronic
T1 In Vivo Disruption of Xenopus CLOCK in the Retinal Photoreceptor Cells Abolishes Circadian Melatonin Rhythmicity without Affecting Its Production Levels
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1600
OP 1607
DO 10.1523/JNEUROSCI.22-05-01600.2002
VO 22
IS 5
A1 Naoto Hayasaka
A1 Silvia I. LaRue
A1 Carla B. Green
YR 2002
UL http://www.jneurosci.org/content/22/5/1600.abstract
AB Xenopuslaevis retinas, like retinas from all vertebrate classes, have endogenous circadian clocks that control many aspects of normal retinal physiology occurring in cells throughout all layers of the retina. The localization of the clock(s) that controls these various rhythms remains unclear. One of the best studied rhythmic events is the nocturnal release of melatonin. Photoreceptor layers can synthesize rhythmic melatonin when these cells are in isolation. However, within the intact retina, melatonin is controlled in a complex way, indicating that signals from many parts of the retina may contribute to the production of melatonin rhythmicity. To test this hypothesis, we generated transgenic tadpoles that express different levels of a dominant negative XenopusCLOCK specifically in the retinal photoreceptors. Eyes from these tadpoles continued to produce melatonin at normal levels, but with greatly disrupted rhythmicity, the severity of which correlated with the transgene expression level. These results demonstrate that although many things contribute to melatonin production in vivo, the circadian clock localized in the retinal photoreceptors is necessary for its rhythmicity. Furthermore, these data show that the control of the level of melatonin synthesis is separable from the control of its rhythmicity and may be controlled by different molecular machinery. This type of specific “molecular lesion” allows perturbation of the clock in intact tissues and is valuable for dissection of clock control of tissue-level processes in this and other complex systems.