title: Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes.
abstract: 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.
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Dorit
authors.initials: D
authors.lastname: Hockman
authors.affiliation: Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Burns
authors.affiliation: School of Natural Sciences, National University of Ireland, Galway, Ireland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schlosser
authors.affiliation: Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Gates
authors.affiliation: Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Jevans
authors.affiliation: Department of Mechanical Engineering, University of California, California NanoSystem Institute, Santa Barbara, United States.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mongera
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, United States.
authors.forename: Shannon
authors.initials: S
authors.lastname: Fisher
authors.affiliation: Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, United States.
authors.forename: Gokhan
authors.initials: G
authors.lastname: Unlu
authors.affiliation: Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, United States.
authors.forename: Ela W
authors.initials: EW
authors.lastname: Knapik
authors.affiliation: Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, United States.
authors.forename: Charles K
authors.initials: CK
authors.lastname: Kaufman
authors.affiliation: Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Mosimann
authors.affiliation: Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States.
authors.forename: Leonard I
authors.identifier: http://orcid.org/0000-0003-0860-926X
authors.initials: LI
authors.lastname: Zon
authors.affiliation: Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lancman
authors.affiliation: Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States.
authors.forename: P Duc S
authors.initials: PDS
authors.lastname: Dong
authors.affiliation: Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
authors.affiliation: Department of Craniofacial Development and Stem Cell Biology, King's College London, London, United Kingdom.
authors.forename: Abigail S
authors.initials: AS
authors.lastname: Tucker
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Clare Vh
authors.identifier: http://orcid.org/0000-0002-4434-3107
authors.initials: CV
authors.lastname: Baker
mesh_terms: D000818:Animals; D001001:Anura; D005075:Biological Evolution; D015687:Cell Hypoxia; D019070:Cell Lineage; D007798:Lampreys; D055099:Neuroendocrine Cells; D046569:Neuroepithelial Cells; D015027:Zebrafish
keywords: carotid body; chicken; developmental biology; endoderm; fate-mapping; mouse; neural crest; neuroepithelial cells; sea lamprey (Petromyzon marinus); stem cells; xenopus; zebrafish