Phox2b controls the development of peripheral chemoreceptors and afferent visceral pathways.
We report that the afferent relays of visceral (cardiovascular, digestive and respiratory) reflexes, differentiate under the control of the paired-like homeobox gene Phox2b: the neural crest-derived carotid body, a chemosensor organ, degenerates in homozygous mutants, as do the three epibranchial placode-derived visceral sensory ganglia (geniculate, petrosal and nodose), while their central target, the nucleus of the solitary tract, which integrates all visceral information, never forms. These data establish Phox2b as an unusual 'circuit-specific' transcription factor devoted to the formation of autonomic reflex pathways. We also show that Phox2b heterozygous mutants have an altered response to hypoxia and hypercapnia at birth and a decreased tyrosine hydroxylase expression in the petrosal chemosensory neurons, thus providing mechanistic insight into congenital central hypoventilation syndrome, which is associated with heterozygous mutations in PHOX2B.
Dauger
Stéphane
S
Laboratoire de Neurologie et Physiologie du Développement, INSERM EPI9935, Hôpital Robert Debré, 48 Bd Serurier, 75019 Paris, France.
Pattyn
Alexandre
A
Lofaso
Frédéric
F
Gaultier
Claude
C
Goridis
Christo
C
Gallego
Jorge
J
Brunet
Jean-François
JF
D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002344:Carotid Body / Q000196:embryology; D002628:Chemoreceptor Cells / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D006935:Hypercapnia / Q000235:genetics; D000860:Hypoxia / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009432:Neural Crest / Q000502:physiology*; D010993:Plethysmography, Whole Body; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000196:embryology; D017552:Solitary Nucleus / Q000196:embryology*; D014157:Transcription Factors / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase