The Journal of Neuroscience, March 1, 2002, 22(5):1600-1607
In Vivo Disruption of Xenopus CLOCK
in the Retinal Photoreceptor Cells Abolishes Circadian Melatonin
Rhythmicity without Affecting Its Production Levels
Naoto
Hayasaka,
Silvia I.
LaRue, and
Carla B.
Green
Department of Biology, National Science Foundation Center
for Biological Timing, University of Virginia, Charlottesville,
Virginia 22904-4328
Xenopus laevis 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 Xenopus
CLOCK 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.
Key words:
dominant negative CLOCK; transgenic Xenopus; circadian clock; retinal photoreceptor; melatonin rhythm; arylalkylamine N-acetyltransferase (AANAT)
Copyright © 2002 Society for Neuroscience 0270-6474/02/2251600-08$05.00/0
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