Hindbrain interneurons and axon guidance signaling critical for breathing

Nat Neurosci. 2010 Sep;13(9):1066-74. doi: 10.1038/nn.2622. Epub 2010 Aug 2.


Breathing is a bilaterally synchronous behavior that relies on a respiratory rhythm generator located in the brainstem. An essential component of this generator is the preBötzinger complex (preBötC), which paces inspirations. Little is known about the developmental origin of the interneuronal populations forming the preBötC oscillator network. We found that the homeobox gene Dbx1 controls the fate of glutamatergic interneurons required for preBötC rhythm generation in the mouse embryo. We also found that a conditional inactivation in Dbx1-derived cells of the roundabout homolog 3 (Robo3) gene, which is necessary for axonal midline crossing, resulted in left-right de-synchronization of the preBötC oscillator. Together, these findings identify Dbx1-derived interneurons as the core rhythmogenic elements of the preBötC oscillator and indicate that Robo3-dependent guidance signaling in these cells is required for bilaterally synchronous activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • Functional Laterality
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Interneurons / physiology*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Motor Neurons / physiology
  • Nerve Tissue Proteins / metabolism
  • Neural Pathways / embryology
  • Neural Pathways / physiology
  • Periodicity
  • Receptors, Cell Surface
  • Respiration*
  • Rhombencephalon / embryology*
  • Rhombencephalon / physiology*


  • Dbx1 protein, mouse
  • Homeodomain Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Robo3 protein, mouse