The preBötzinger complex (preBötC) is a critical component of the respiratory rhythm–generator that underlies mammalian breathing. However, we know little about the developmental origins of its neurons or the molecular mechanisms that determine their fate. Anatomically, it is characterized as a collection of glutamatergic interneurons that express the neurokinin type1 receptor (NK1R) and somatostatin (Sst). These glutamatergic interneurons are rhythmically active and are indispensable for the generation of the respiratory rhythm. They also project across the midline, connecting the two halves of the preBötC to establish bilateral synchrony, which is critical for efficient breathing.

On page 1066, Bouvier and colleagues identified the homeobox gene Dbx1 as being critical for controlling the fate of these glutmatergic interneurons. Using a genetic strategy, supported by molecular and electrophysiological techniques, they found that Dbx1-expressing progenitors give rise to the glutamatergic interneurons that are necessary for rhythm generation and bilateral synchrony of the preBötC, including the constitutive NK1R- and Sst-expressing neurons, and that Dbx1 is critical for establishing their fate during embryonic development. Moreover, they found that the establishment of commissural connections between the halves of the preBötC requires expression of the Robo3 receptor by the Dbx1-derived interneurons. A coronal section of the mouse embryonic medulla is shown in which commissural connections are made by biocytin-labeled interneurons (green) projecting to the vicinity of the contralateral NK1R-positive neurons of the preBötC (red) near the nucleus ambiguus (labeled blue).