Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice.
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.DOI: http://dx.doi.org/10.7554/eLife.02265.001.
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, United States.
Srinivasan
S
Tupal
Program in Developmental Biology, Baylor College of Medicine, Houston, United States Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, United States.
Wei-Hsiang
WH
Huang
Department of Applied Science, The College of William and Mary, Williamsburg, United States.
Maria Cristina D
http://orcid.org/0000-0001-8912-2175
MC
Picardo
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, United States.
Guang-Yi
GY
Ling
Department of Applied Science, The College of William and Mary, Williamsburg, United States.
Christopher A
http://orcid.org/0000-0002-7848-8224
CA
Del Negro
Program in Developmental Biology, Baylor College of Medicine, Houston, United States Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Baylor College of Medicine, Houston, United States Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.
Huda Y
HY
Zoghbi
Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, United States pgray@pcg.wustl.edu.
Paul A
PA
Gray
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D018398:Homeodomain Proteins / Q000502:physiology; D008046:Lip / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D012143:Respiratory Physiological Phenomena; D012249:Rhombencephalon / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; C500943:Atoh1 protein, mouse; C103403:Dbx1 protein, mouse
PreBötzinger Complex; breathing; central pattern generator; oscillator; transcription