We sequenced the transcriptome of brainstem interneurons in the specialized respiratory rhythmogenic site dubbed preBotzinger Complex (preBotC) from newborn mice. To distinguish molecular characteristics of the core oscillator we compared preBotC neurons derived from Dbx1-expressing progenitors that are respiratory rhythmogenic to neighbouring non-Dbx1-derived neurons, which support other respiratory and non-respiratory functions. Results in three categories are particularly salient. First, Dbx1 preBotC neurons express kappa-opioid receptors in addition to mu-opioid receptors that heretofore have been associated with opiate respiratory depression, which may have clinical applications. Second, Dbx1 preBotC neurons express the hypoxia-inducible transcription factor Hif1a at levels three-times higher than non-Dbx1 neurons, which links core rhythmogenic microcircuits to O-2-related chemosensation for the first time. Third, we detected a suite of transcription factors including Hoxa4 whose expression pattern may define the rostral preBotC border, Pbx3 that may influence ipsilateral connectivity, and Pax8 that may pertain to a ventrally-derived subset of Dbx1 preBotC neurons. These data establish the transcriptomic signature of the core respiratory oscillator at a perinatal stage of development.
Hayes, John A.; Kottick, Andrew; Picardo, Maria Cristina D.; Halleran, Andrew D.; Smith, Ronald D.; Smith, Gregory D.; Saha, Margaret S.; and Del Negro, Christopher A., Transcriptome of Neonatal PreBotzinger Complex Neurones in Dbx1 Reporter Mice (2017). Scientific Reports, 7, 8669.