Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes.

Dorit Hockman,Abigail S Tucker,Gokhan Unlu,Gerhard Schlosser,Leonard I Zon,Shannon Fisher,Charles K Kaufman,Heiko Lickert,Joseph J Lancman,Ela W Knapik,Benjamin Jevans,Keith P Gates,Clare V H Baker,Christian Mosimann,Alan J Burns,Alessandro Mongera,P Duc S Dong

doi:10.7554/elife.21231

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.

Highlights

During hypoxia in vertebrates, respiratory reflexes such as hyperventilation are triggered by neurotransmitter release from hypoxia-sensitive serotonergic cells associated with pharyngeal arch arteries, as well as in the lungs and/or gills
Carotid body glomus cells develop from the neural crest (Le Douarin et al, 1972; Pearse et al, 1973; Pardal et al, 2007), while pulmonary neuroendocrine cells’ (PNECs) differentiate in situ within pulmonary airway epithelia (Hoyt et al, 1990; Rawlins et al, 2009; Song et al, 2012; Kuo and Krasnow, 2015)
Glomus cells are neural crest-derived (Le Douarin et al, 1972; Pearse et al, 1973; Pardal et al, 2007) and the hypothesis is not compatible with our demonstration that neural crest cells do not contribute to gill neuroepithelial cells’ (NECs) in zebrafish, or their presumed homologues in Xenopus and lamprey, or to similar innervated serotonergic cells in the orobranchial epithelium of all three anamniote species

Summary

Introduction

Respiratory reflexes such as hyperventilation are triggered by neurotransmitter release from hypoxia-sensitive serotonergic cells associated with pharyngeal arch arteries, as well as in the lungs and/or gills (reviewed by Lopez-Barneo et al, 2016; Cutz et al, 2013; Jonz et al, 2016). Glomus cells respond to hypoxia in arterial blood by releasing stored neurotransmitters including acetylcholine, ATP, the catecholamine dopamine, and serotonin (the latter two most likely acting as autocrine/paracrine neuromodulators) (reviewed by Nurse and Piskuric, 2013; Nurse, 2014) These excite afferent terminals of the carotid sinus nerve (a branch of the glossopharyngeal nerve, arising from neurons in the petrosal ganglion) in mammals (reviewed by Nurse and Piskuric, 2013; Nurse, 2014), and of the vagal nerve (arising from neurons in the nodose ganglion) in birds (Kameda, 2002). PNECs provide an important stem-cell niche for regenerating the airway epithelium after injury (Reynolds et al, 2000; Guha et al, 2012; Song et al, 2012) and were recently shown to be the predominant cells of origin for small cell lung cancer (Park et al, 2011; Sutherland et al, 2011; Song et al, 2012)

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