Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes
Dorit Hockman,
Alan J Burns,
Gerhard Schlosser,
Keith P Gates,
Benjamin Jevans,
Alessandro Mongera,
Shannon Fisher,
Gokhan Unlu,
Ela W Knapik,
Charles K Kaufman,
Christian Mosimann,
Leonard I Zon,
Joseph J Lancman,
P Duc S Dong,
Heiko Lickert,
Abigail S Tucker,
Clare V H Baker
Affiliations
Dorit Hockman
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom; Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom; Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa
Alan J Burns
Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
Gerhard Schlosser
School of Natural Sciences, National University of Ireland, Galway, Ireland
Keith P Gates
Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States
Benjamin Jevans
Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
Alessandro Mongera
Department of Genetics, Max-Planck Institut für Entwicklungsbiologie, Tübingen, Germany
Shannon Fisher
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, United States
Gokhan Unlu
Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States
Ela W Knapik
Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, United States
Charles K Kaufman
Children’s Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States
Christian Mosimann
Children’s Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States
The 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.
