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First published online 19 November 2003
doi: 10.1242/dev.00866

Development 130, 6635-6642 (2003)
Published by The Company of Biologists 2003
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Research Article: Development and Disease

Phox2b controls the development of peripheral chemoreceptors and afferent visceral pathways

Stéphane Dauger1,*, Alexandre Pattyn2,*, Frédéric Lofaso1, Claude Gaultier1, Christo Goridis2, Jorge Gallego1 and Jean-François Brunet2,{dagger}

1 Laboratoire de Neurologie et Physiologie du Développement, INSERM EPI9935, Hôpital Robert Debré, 48 Bd Serurier, 75019 Paris, France
2 CNRS UMR 8542, Département de Biologie, Ecole Normale Supérieure, 46 rue d'Ulm, 75005 Paris, France

{dagger} Author for correspondence (e-mail: jfbrunet{at}biologie.ens.fr)

Accepted 15 September 2003

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.

Key words: Transcription factor, Autonomic nervous system, Sensory neurons


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