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Otx5 regulates genes that show circadian expression in the zebrafish pineal complex

Nature Genetics volume 30, pages 117–121 (2002)Cite this article

Abstract

The photoneuroendocrine system translates environmental light conditions into the circadian production of endocrine and neuroendocrine signals. Central to this process is the pineal organ, which has a conserved role in the cyclical synthesis and release of melatonin to influence sleep patterns and seasonal reproduction1. In lower vertebrates, the pineal organ contains photoreceptors whose activity entrains an endogenous circadian clock and regulates transcription in pinealocytes1. In mammals, pineal function is influenced by retinal photoreceptors that project to the suprachiasmatic nucleus—the site of the endogenous circadian clock. A multisynaptic pathway then relays information about circadian rhythmicity and photoperiod to the pineal organ1. The gene cone rod homeobox (crx), a member of the orthodenticle homeobox (otx) family, is thought to regulate pineal circadian activity. In the mouse, targeted inactivation of Crx causes a reduction in pineal gene expression and attenuated entrainment to light/dark cycles2. Here we show that crx and otx5 orthologs are expressed in both the pineal organ and the asymmetrically positioned parapineal of larval zebrafish. Circadian gene expression is unaffected by a reduction in Crx expression but is inhibited specifically by depletion of Otx5. Our results indicate that Otx5 rather than Crx regulates genes that show circadian expression in the zebrafish pineal complex.

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Figure 1: Identity of zebrafish orthodenticle-related homeobox 5 (Otx5).
Figure 2: Expression of otx5 in the pineal complex of wildtype (WT) and mutant larvae.
Figure 3: Mutant larvae show circadian-regulated gene expression.
Figure 4: Retinal but not pineal gene expression is reduced by Crx depletion.
Figure 5: Expression of circadian-regulated genes is lost in Otx5-depleted larvae.
Figure 6: Otx 5 is required for rhythmic gene expression throughout the circadian cycle.

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Acknowledgements

We thank M. Macurak, J. Prowell and L. Hantsoo for technical help. This work was supported by an American Cancer Society postdoctoral fellowship (J.T.G.), the Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Hôpital Universitaire de Strasbourg, Association pour la Recherche sur le Cancer, Ligue Nationale Contre le Cancer (C.T., B.T.), NIH grants (C.T., B.T., P.A.R.) and an NRSA fellowship (J.O.L.).

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Authors and Affiliations

  1. Department of Embryology, Carnegie Institution of Washington, Baltimore, 21210, Maryland, USA

    Joshua T. Gamse, Marnie E. Halpern & Jennifer O. Liang

  2. Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Yu-Chi Shen & Pamela A. Raymond

  3. Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP CU de Strasbourg, Illkirch Cedex, 67404, Strasbourg, France

    Christine Thisse & Bernard Thisse

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Correspondence to Marnie E. Halpern.

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Gamse, J., Shen, YC., Thisse, C. et al. Otx5 regulates genes that show circadian expression in the zebrafish pineal complex. Nat Genet 30, 117–121 (2002). https://doi.org/10.1038/ng793

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