Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant

  1. Mariko Izumo
  2. Martina Pejchal
  3. Andrew C Schook
  4. Ryan P Lange
  5. Jacqueline A Walisser
  6. Takashi R Sato
  7. Xiaozhong Wang
  8. Christopher A Bradfield
  9. Joseph S Takahashi  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. Northwestern University, United States
  3. University of Wisconsin, United States
  4. University of Tübingen, Germany
  5. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, United States

Abstract

In order to assess the contribution of a central clock in the hypothalamic suprachiasmatic nucleus (SCN) to circadian behavior and the organization of peripheral clocks, we generated forebrain/SCN-specific Bmal1 knockout mice by using floxed Bmal1 and pan-neuronal Cre lines. The forebrain knockout mice showed >90% deletion of BMAL1 in the SCN and exhibited an immediate and complete loss of circadian behavior in constant conditions. Circadian rhythms in peripheral tissues persisted, but became desynchronized and damped in constant darkness. The loss of synchrony was rescued by light/dark cycles, and partially by restricted feeding (only in the liver and kidney but not in the other tissues) in a distinct manner. These results suggest that the forebrain/SCN is essential for internal temporal order of robust circadian programs in peripheral clocks and that individual peripheral clocks are affected differently by light and feeding in the absence of a functional oscillator in the forebrain.

Article and author information

Author details

  1. Mariko Izumo

    Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Martina Pejchal

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Andrew C Schook

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ryan P Lange

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jacqueline A Walisser

    McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Takashi R Sato

    Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Xiaozhong Wang

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Christopher A Bradfield

    McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Joseph S Takahashi

    Department of Neuroscience, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    joseph.takahashi@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal care and use procedures were in accordance with guidelines of the Northwestern University (Protocol 2006-0035) and UT Southwestern Institutional Animal Care and Use Committees (Protocols 2009-0054 and 2012-0090).

Reviewing Editor

  1. Louis Ptáček, University of California, San Francisco, United States

Publication history

  1. Received: September 9, 2014
  2. Accepted: December 18, 2014
  3. Accepted Manuscript published: December 19, 2014 (version 1)
  4. Version of Record published: January 21, 2015 (version 2)

Copyright

© 2014, Izumo et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Mariko Izumo
  2. Martina Pejchal
  3. Andrew C Schook
  4. Ryan P Lange
  5. Jacqueline A Walisser
  6. Takashi R Sato
  7. Xiaozhong Wang
  8. Christopher A Bradfield
  9. Joseph S Takahashi
(2014)
Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant
eLife 3:e04617.
https://doi.org/10.7554/eLife.04617
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