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Oscillatory Mechanisms Underlying the Murine Circadian Clock

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Science's STKE  18 Nov 2003:
Vol. 2003, Issue 209, pp. tr7
DOI: 10.1126/stke.2092003tr7

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  • Oscillatory Mechanisms Underlying the Murine Circadian Clock

    Russell N. Van Gelder1* and Erik D. Herzog2

    1Department of Ophthalmology and Visual Sciences, Department of Molecular Biology and Pharmacology, Washington University Medical School, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

    2Department of Biology, Washington University, St. Louis, MO 63130, USA.


    *Contact information. E-mail, vangelder{at}vision.wustl.edu


    This animation depicts a schematic of the murine circadian clock mechanism in a single, pacemaking neuron in the suprachiasmatic nucleus (SCN) of the hypothalamus, where the master pacemaker is located. Circadian clocks allow organisms to display behaviors and processes with a 24-hour rhythm even in the absence of light input. The basic molecular mechanism consists of two intertwined transcription-translation negative feedback loops. One loop--the "positive loop"--controls the rhythmic expression of a positive transcription factor gene, Bmal1 (also called Mop3). The second loop--the "negative loop"--controls the transcription of genes in the Period and Cryptochrome families, which encode repressor proteins. The loops are intertwined because the proteins PERIOD and CRYPTOCHROME directly repress transcription mediated by the transcription factors CLOCK and BMAL1, whereas the CLOCK:BMAL1 heterodimer drives transcription of the Period and Cryptochrome genes, as well as that of Rev-erb-alpha, which represses Bmal1 expression. Other proteins, such as casein kinase I ε (CKIε) play essential modulatory roles in mammalian circadian timekeeping.

    The time of day is represented as Zeitgeber time (ZT), which is the number of hours elapsed since dawn (ZT 0), and is indicated by the travel of the sun and moon. ZT 6 corresponds to noon, ZT 12 to dusk, and ZT 18 to midnight. Within each cell, circadian clock components are shown in the cytoplasm (black) and nucleus (dark blue). Each gene's coding DNA is color coded as double helical, whereas the transcripts from that gene are shown as blue curved lines. The changes in abundance and interactions of many components of the oscillatory mechanism occur simultaneously; for simplicity, the major activities taking place at each time point are listed.

    The animation accompanying each interaction can be seen individually by clicking on the green arrow. The times shown for all activities are approximate, and may vary from cell to cell within a single organism. To see the animation in continuous motion, click and hold the red double arrows at the bottom of the screen.

    The animation was created by Cameron Slayden under the scientific oversight of Russell N. Van Gelder, Department of Ophthalmology and Visual Sciences, Department of Molecular Biology and Pharmacology, Washington University Medical School, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

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    Educational Details

    Learning Resource Type: Animation

    Context: Undergraduate upper division, graduate, professional (degree program)

    Intended Users: Teacher, learner

    Intended Educational Use: Teach, learn

    Discipline: Cell Biology, Physiology, Neurobiology

    Keywords: movie, mouse, circadian, clock, rhythm

    Technical Details

    Format: Shockwave Flash Object (swf file)

    Size: 68 kb

    Requirements: Macromedia Flash 5 (http://www.macromedia.com/downloads/)

    Related Resources

    Connections Map: R. N. Van Gelder, Murine circadian pathway. Sci. STKE (as seen November 2003), http://stke.sciencemag.org/cgi/cm/CMP_ 13010. [Abstract] [Specific Pathway]

    Connections Map: Russell N. Van Gelder, Circadian pathway. Sci. STKE (as seen November 2003), http://stke.sciencemag.org/cgi/cm/stkecm;CMP_12992. [Abstract] [Canonical Pathway]

    Review: M. P. Pando, P. Sassone-Corsi, Signaling to the mammalian circadian clocks: In pursuit of the primary mammalian circadian photoreceptor. Sci. STKE 2001, re16 (2001). [Gloss] [Abstract] [Full Text]

    Virtual Journal: R. N. Van Gelder, E. D. Herzog, W. J. Schwartz, P. H. Taghert, Circadian rhythms: In the loop at last. Science 300, 1534-1535 (2003). [Abstract] [Full Text]

    Limits for Use

    Cost: Free

    Rights: This material may be downloaded, printed, linked to, and/or redistributed without modification for noncommercial, course-teaching purposes only, provided credit to STKE is included by listing the citation for the teaching resource.


    Citation: R. N. Van Gelder, Oscillatory Mechanisms Underlying the Murine Circadian Clock, Sci. STKE2003, tr7 (2003).

    © 2003 American Association for the Advancement of Science

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