1. Neuroscience
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Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice

  1. Srinivasan Tupal
  2. Wei-Hsiang Huang
  3. Maria CD Picardo
  4. Guang-Yi Ling
  5. Christopher A Del Negro
  6. Huda Y Zoghbi
  7. Paul A Gray  Is a corresponding author
  1. University of Virginia, United States
  2. Howard Hughes Medical Institute, Stanford University, United States
  3. The College of William and Mary, United States
  4. Washington University School of Medicine, United States
  5. Howard Hughes Medical Institute, Baylor College of Medicine, United States
Research Article
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Cite this article as: eLife 2014;3:e02265 doi: 10.7554/eLife.02265

Abstract

All motor behaviors require precise temporal coordination of different muscle groups. Breathing, for example, involves the sequential activation of numerous muscles hypothesized to be driven by a primary respiratory oscillator, the preBötzinger Complex, and at least one other as-yet unidentified rhythmogenic population. We tested the roles of Atoh1-, Phox2b-, and Dbx1-derived neurons (three groups that have known roles in respiration) in the generation and coordination of respiratory output. We found that Dbx1-derived neurons are necessary for all respiratory behaviors, whereas independent but coupled respiratory rhythms persist from at least three different motor pools after eliminating or silencing Phox2b- or Atoh1-expressing hindbrain neurons. Without Atoh1 neurons, however, the motor pools become temporally disorganized and coupling between independent respiratory oscillators decreases. We propose Atoh1 neurons tune the sequential activation of independent oscillators essential for the fine control of different muscles during breathing.

Article and author information

Author details

  1. Srinivasan Tupal

    University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.
  2. Wei-Hsiang Huang

    Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  3. Maria CD Picardo

    The College of William and Mary, Williamsburg, United States
    Competing interests
    No competing interests declared.
  4. Guang-Yi Ling

    Washington University School of Medicine, Saint Louis, United States
    Competing interests
    No competing interests declared.
  5. Christopher A Del Negro

    The College of William and Mary, Williamsburg, United States
    Competing interests
    No competing interests declared.
  6. Huda Y Zoghbi

    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States
    Competing interests
    Huda Y Zoghbi, Senior editor, eLife.
  7. Paul A Gray

    Washington University School of Medicine, Saint Louis, United States
    For correspondence
    pgray@pcg.wustl.edu
    Competing interests
    No competing interests declared.

Ethics

Animal experimentation: Experiments were done in accordance with the Institute for Laboratory Animal Research Guide for the Care and Use of Laboratory Animals. All experiments were approved by the Animal Studies Committee at Washington University School of Medicine (protocol # 20110249), the Institutional Animal Care and Use Committee at the College of William and Mary, and the Center for Comparative Medicine, Baylor College of Medicine.

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Publication history

  1. Received: January 10, 2014
  2. Accepted: May 13, 2014
  3. Accepted Manuscript published: May 14, 2014 (version 1)
  4. Version of Record published: June 17, 2014 (version 2)

Copyright

© 2014, Tupal 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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