Hockman, DoritBurns, Alan JSchlosser, GerhardGates, Keith PJevans, BenjaminMongera, AlessandroFisher, ShannonUnlu, GokhanKnapik, Ela WKaufman, Charles KMosimann, ChristianZon, LeonardLancman, Joseph JDong, P Duc SLickert, HeikoTucker, Abigail SBaker, Clare V H2017-06-152017Hockman, D., A. J. Burns, G. Schlosser, K. P. Gates, B. Jevans, A. Mongera, S. Fisher, et al. 2017. “Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes.” eLife 6 (1): e21231. doi:10.7554/eLife.21231. http://dx.doi.org/10.7554/eLife.21231.http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029918The evolutionary origins of the hypoxia-sensitive cells that trigger amniote respiratory reflexes – carotid body glomus cells, and ‘pulmonary neuroendocrine cells’ (PNECs) - are obscure. Homology has been proposed between glomus cells, which are neural crest-derived, and the hypoxia-sensitive ‘neuroepithelial cells’ (NECs) of fish gills, whose embryonic origin is unknown. NECs have also been likened to PNECs, which differentiate in situ within lung airway epithelia. Using genetic lineage-tracing and neural crest-deficient mutants in zebrafish, and physical fate-mapping in frog and lamprey, we find that NECs are not neural crest-derived, but endoderm-derived, like PNECs, whose endodermal origin we confirm. We discover neural crest-derived catecholaminergic cells associated with zebrafish pharyngeal arch blood vessels, and propose a new model for amniote hypoxia-sensitive cell evolution: endoderm-derived NECs were retained as PNECs, while the carotid body evolved via the aggregation of neural crest-derived catecholaminergic (chromaffin) cells already associated with blood vessels in anamniote pharyngeal arches. DOI: http://dx.doi.org/10.7554/eLife.21231.001en-USsea lamprey (Petromyzon marinus)neural crestendodermneuroepithelial cellscarotid bodyfate-mappingChickenMouseOtherZebrafishJournal Article2017-06-1510.7554/eLife.21231