on behalf of the American Thoracic Society/ European Respiratory Society Working Group on Infant and Young Children Pulmonary Function Testing This official statement of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) was approved by the ATS Board of Directors, September 2006, and the ERS Executive Committee, December 2006 6. Further multidisciplinary work is required to investigate the best combination of tests (e.g., structure, function, inflammation, atopy) and challenges (e.g., pharmaceutical vs. physical) to investigate specific clinical entities during early childhood.
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.
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