Hindbrain interneurons and axon guidance signaling critical for breathing.
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.
Bouvier
Julien
J
Institut de Neurobiologie Alfred Fessard, CNRS UPR 3294, Gif-sur-Yvette, France.
Thoby-Brisson
Muriel
M
Renier
Nicolas
N
Dubreuil
Véronique
V
Ericson
Johan
J
Champagnat
Jean
J
Pierani
Alessandra
A
Chédotal
Alain
A
Fortin
Gilles
G
D000818:Animals; D001369:Axons / Q000502:physiology*; D007839:Functional Laterality; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000196:embryology / Q000502:physiology; D010507:Periodicity; D011956:Receptors, Cell Surface; D012119:Respiration; D012249:Rhombencephalon / Q000196:embryology* / Q000502:physiology*; D000097905:Roundabout Proteins
D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; C103403:Dbx1 protein, mouse; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins