We breathe roughly half a billion times in a lifetime, generally in an effortless and even unconscious manner owing to activity of a respiratory central pattern generator (CPG) located in the hindbrain. The respiratory CPG relies on the coupling of two prominent rhythmogenic sites located in the medulla, the pre-Bötzinger Complex (preBötC) and the retrotrapezoid nucleus/para-Facial Respiratory Group (RTN). Working in the mouse embryo, we have identified the emergence of embryonic versions of these two oscillators using developmental genetics tools, electrophysiological and optical recordings. We have recently defined molecular and functional signatures for cells composing each oscillator. The talk will focus on the embryonic version of the RTN, an Egr2- (also known as Krox20-) derived, Lbx1-/Atoh1- and Phox2b-expressing group of cells located at the ventral surface of the brainstem below the facial motor nucleus. Mutations in the neuron type-specific homeogene Phox2b are causative for central congenital hypoventilation syndrome (CCHS). Introducing one of the most common human mutations (Phox2b27Ala ) in mouse leads to a CCHS-like respiratory syndrome, including apneas, arythmia, and unresponsiveness to a hypercapnic challenge —and neonatal death. This mutation preserves many Phox2b-positive neural structures, but destroys the retrotrapezoid nucleus (RTN). Similarly, Atoh1 null mutants feature a disrupted RTN and die at birth. Electrophysiological studies have implicated the RTN in central CO2 sensitivity and perinatal entrainment of the preBötC and downstream inspiratory outputs. We have confirmed this at embryonic stages using an optogenetic approach and patterned light photostimulation targeting RTN neurons. Altogether, these data point to the RTN as a major culprit in CCHS pathogenesis. However, we also found that spatially limited expression of the Phox2b27Ala allele can be compatible with life, while nevertheless destroying the RTN and abolishing the perinatal hypercapnic response. Thus, the central chemoreflex is dispensable for neonatal life and defects in Phox2b-expressing neurons outside the RTN contribute to the full CCHS-like syndrome in mouse.