Hindbrain Interneurons and Axon Guidance Signalling Critical for Breathing
Résumé
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) that paces inspirations. Little is known about the developmental origin of interneuronal populations forming the preBötC oscillator network. We show that the homeobox gene Dbx1 controls the fate of glutamatergic interneurons required for preBötC rhythm generation in the mouse embryo. We also show that a conditional inactivation in Dbx1-derived cells of the Roundabout receptor 3 (Robo3) gene, necessary for axonal midline crossing, results 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 Robo3-dependent guidance signaling in these cells as a requirement for bilaterally synchronous activity.
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