Research in animal models implicates the retrotrapezoid nucleus (RTN) as a critical central chemoreceptor located in the brain stem. In rodents, RTN neurons co-express the tachykinin receptor NK1R and the transcription factor PHOX2B. In humans, PHOX2B mutations, which expand a polyalanine tract in the protein, cause congenital central hypoventilation syndrome. Mice with analogous Phox2B mutations model this phenotype and lack PHOX2B immunoreactivity in their RTNs. We evaluated PHOX2B immunoreactivity in sections of the caudal pons and medulla of 17 human fetuses and infants. The transcription factor was detected in brain stem nuclei that correspond to established sites of murine PHOX2B expression, including the RTN. The putative human RTN is located ventral to the facial nucleus and lateral to the superior olivary nucleus at the level of the pontomedullary junction.
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