Central chemoreception: Lessons from mouse and human genetics

The response to increased PCO2PCO2 in the brain is an essential drive to breathe and required for CO2 and pH homeostasis in the blood, but where and how CO2 is sensed are still contentious issues. Here, we review evidence from mouse and human genetics that argue for the crucial role in CO2 chemosensitivity of a limited set of central neurons that express the Phox2b transcription factor and are disabled by Phox2b mutations. A common trait of different Phox2b mutations that impair CO2 responsiveness in the embryo and respiration in neonates is the depletion of Phox2b-expressing neurons in the retrotrapezoid nucleus, providing genetic evidence for their importance for proper breathing and central chemosensitivity at birth.