Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-26T07:09:12.117Z Has data issue: false hasContentIssue false

Expression of circadian clock genes in retinal dopaminergic cells

Published online by Cambridge University Press:  17 August 2007

RONALD DORENBOS
Affiliation:
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts
MASSIMO CONTINI
Affiliation:
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts Università di Firenze, Dipartimento di Anatomia, Istologia e Medicina Ljegale, Italy
HAJIME HIRASAWA
Affiliation:
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts
STEFANO GUSTINCICH
Affiliation:
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts Department of Neurobiology, SISSA/ISAS, Trieste, Italy
ELIO RAVIOLA
Affiliation:
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts

Abstract

The mammalian neural retina contains single or multiple intrinsic circadian oscillators that can be directly entrained by light cycles. Dopaminergic amacrine (DA) cells represent an especially interesting candidate as a site of the retinal oscillator because of the crucial role of dopamine in light adaptation, and the widespread distribution of dopamine receptors in the retina. We hereby show by single-cell, end-point RT-PCR that retinal DA cells contain the transcripts for six core components of the circadian clock: Bmal1, Clock, Cry1, Cry2, Per1, and Per2. Rod photoreceptors represented a negative control, because they did not appear to contain clock transcripts. We finally confirmed that DA cells contain the protein encoded by the Bmal1 gene by comparing immunostaining of the nuclei of DA cells in the retinas of wildtype and Bmal1−/− mice. It is therefore likely that DA cells contain a circadian clock that anticipates predictable variations in retinal illumination.

Type
Research Article
Copyright
© 2007 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Besharse, J.C. & Iuvone, P.M. (1983). Circadian clock in Xenopus eye controlling retinal serotonin N-acetyltransferase. Nature 305, 133135.CrossRefGoogle Scholar
Besharse, J.C., Hollyfield, J.G. & Rayborn, M.E. (1977). Turnover of rod photoreceptor outer segments. II. Membrane addition and loss in relationship to light. Journal of Cell Biology 75, 507527.Google Scholar
Bunger, M.K., Wilsbacher, L.D., Moran, S.M., Clendenin, C., Radcliffe, L.A., Hogenesch, J.B., Simon, M.C., Takahashi, J.S. & Bradfield, C.A. (2000). Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103, 10091017.CrossRefGoogle Scholar
Cahill, G.M. & Besharse, J.C. (1993). Circadian clock functions localized in Xenopus retinal photoreceptors. Neuron 10, 573577.CrossRefGoogle Scholar
Contini, M. & Raviola, E. (2003). GABAergic synapses made by a retinal dopaminergic neuron. Proceedings of the National Academy of Sciences of the United States of America 100, 13581363.CrossRefGoogle Scholar
De Waele, P., De Groote, G., Van de Voorde, A., Fiers, W., Franssen, J.-D., Herion, P. & Urbain, J. (1982). Isolation and identification of monoclonal antibodies directed against human placental alkaline phosphatase. Archives Internationales de Physiologie et de Biochimie 90, B21.Google Scholar
Dmitriev, A.V. & Mangel, S.C. (2001). Circadian clock regulation of pH in the rabbit retina. Journal of Neuroscience 21, 28972902.Google Scholar
Doyle, S.E., Grace, M.S., McIvor, W. & Menaker, M. (2002). Circadian rhythms of dopamine in mouse retina: The role of melatonin. Visual Neuroscience 19, 593601.CrossRefGoogle Scholar
Gustincich, S., Feigenspan, A., Wu, D.K., Koopman, L.J. & Raviola, E. (1997). Control of dopamine release in the retina: A transgenic approach to neural networks. Neuron 18, 723736.CrossRefGoogle Scholar
Gustincich, S., Contini, M., Gariboldi, M., Puopolo, M., Kadota, K., Bono, H., LeMieux, J., Walsh, P., Carninci, P., Hayashizaki, Y., Okazaki, Y. & Raviola, E. (2004). Gene discovery in genetically labeled single dopaminergic neurons of the retina. Proceedings of the National Academy of Sciences of the United States of America 101, 50695074.CrossRefGoogle Scholar
Iuvone, P.M., Bernard, M., Alonso-Gomez, A., Greve, P., Cassone, V.M. & Klein, D.C. (1997). Cellular and molecular regulation of serotonin N-acetyltransferase activity in chicken retinal photoreceptors. Biological Signals 6, 217224.Google Scholar
Jaliffa, C.O., Lacoste, F.F., Llomovatte, D.W., Sarmiento, M.I. & Rosenstein, R.E. (2000). Dopamine decreases melatonin content in golden hamster retina. Journal of Pharmacology and Experimental Therapy 293, 9195.Google Scholar
Miyamoto, Y. & Sancar, A. (1998). Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals. Proceedings of the National Academy of Sciences of the United States of America 95, 60976102.CrossRefGoogle Scholar
Pierce, M.E. & Besharse, J.C. (1988). Circadian regulation of retinomotor movements: II. The role of GABA in the regulation of cone position. Journal of Comparative Neurology 270, 279287.Google Scholar
Pierce, M.E., Sheshberadaran, H., Zhang, Z., Fox, L.E., Applebury, M.L. & Takahashi, J.S. (1993). Circadian regulation of iodopsin gene expression in embryonic photoreceptors in retinal cell culture. Neuron 10, 579584.CrossRefGoogle Scholar
Reppert, S.M. & Weaver, D.R. (2001). Molecular analysis of mammalian circadian rhythms. Annual Review of Physiology 63, 647676.CrossRefGoogle Scholar
Reppert, S.M. & Weaver, D.R. (2002). Coordination of circadian timing in mammals. Nature 418, 935941.CrossRefGoogle Scholar
Ribelayga, C. & Mangel, S.C. (2003). Absence of circadian clock regulation of horizontal cell gap junctional coupling reveals two dopamine systems in the goldfish retina. Journal of Comparative Neurology 467, 243253.CrossRefGoogle Scholar
Ribelayga, C., Wang, Y. & Mangel, S.C. (2002). Dopamine mediates circadian clock regulation of rod and cone input to fish retinal horizontal cells. Journal of Physiology 544, 801816.CrossRefGoogle Scholar
Ruan, G.X., Zhang, D.Q., Zhou, T., Yamazaki, S. & McMahon, D.G. (2006). Circadian organization of the mammalian retina. Proceedings of the National Academy of Sciences of the United States of America 103, 97039708.CrossRefGoogle Scholar
Sambrook, J., Fritsch, E.F. & Maniatis, T. (1989). In: Molecular Cloning, A Laboratory Manual, eds. Ford, N., Nolan, C. & Ferguson, M. New York: Cold Spring Harbor Laboratory Press.
Tosini, G. & Fukuhara, C. (2003). Photic and circadian regulation of retinal melatonin in mammals. Journal of Neuroendocrinology 15, 364369.CrossRefGoogle Scholar
Tosini, G. & Menaker, M. (1996). Circadian rhythms in cultured mammalian retina. Science 272, 419421.CrossRefGoogle Scholar
von Schantz, M., Lucas, R.J. & Foster, R.G. (1999). Circadian oscillation of photopigment transcript levels in the mouse retina. Brain Research Molecular Brain Research 72, 108114.CrossRefGoogle Scholar
Witkovsky, P. (2004). Dopamine and retinal function. Documenta Ophthalmologica 108, 1740.CrossRefGoogle Scholar
Witkovsky, P., Veisenberger, E., LeSauter, J., Yan, L., Johnson, M., Zhang, D.Q., McMahon, D. & Silver, R. (2003). Cellular location and circadian rhythm of expression of the biological clock gene Period 1 in the mouse retina. Journal of Neuroscience 23, 76707676.Google Scholar
Zhang, D.-Q., Zhou, T.-R. & McMahon, D.G. (2007). Functional heterogeneity of retinal dopaminergic neurons underlying their multiple roles in vision. Journal of Neuroscience 27, 692699.CrossRefGoogle Scholar
Ziv, L., Levkovitz, S., Toyama, R., Falcon, J. & Gothilf, Y. (2005). Functional development of the zebrafish pineal gland: Light-induced expression of period2 is required for onset of the circadian clock. Journal of Neuroendocrinology 17, 314320.CrossRefGoogle Scholar