Striking parallels between carotid body glomus cell and adrenal chromaffin cell development

Dorit Hockman,Igor Adameyko,Marketa Kaucka,Perrine Barraud,Tomoki Otani,Adam Hunt,Anna C Hartwig,Elisabeth Sock,Dominic Waithe,Marina C.M Franck,Patrik Ernfors,Sean Ehinger,Marthe J Howard,Naoko Brown,Jeffrey Reese,Clare V.H Baker

doi:10.1016/j.ydbio.2018.05.016

Abstract

Carotid body glomus cells mediate essential reflex responses to arterial blood hypoxia. They are dopaminergic and secrete growth factors that support dopaminergic neurons, making the carotid body a potential source of patient-specific cells for Parkinson's disease therapy. Like adrenal chromaffin cells, which are also hypoxia-sensitive, glomus cells are neural crest-derived and require the transcription factors Ascl1 and Phox2b; otherwise, their development is little understood at the molecular level. Here, analysis in chicken and mouse reveals further striking molecular parallels, though also some differences, between glomus and adrenal chromaffin cell development. Moreover, histology has long suggested that glomus cell precursors are ‘émigrés’ from neighbouring ganglia/nerves, while multipotent nerve-associated glial cells are now known to make a significant contribution to the adrenal chromaffin cell population in the mouse. We present conditional genetic lineage-tracing data from mice supporting the hypothesis that progenitors expressing the glial marker proteolipid protein 1, presumably located in adjacent ganglia/nerves, also contribute to glomus cells. Finally, we resolve a paradox for the ‘émigré’ hypothesis in the chicken - where the nearest ganglion to the carotid body is the nodose, in which the satellite glia are neural crest-derived, but the neurons are almost entirely placode-derived - by fate-mapping putative nodose neuronal 'émigrés' to the neural crest.

Highlights

The carotid body is the primary site for monitoring arterial blood hypoxia and hypercapnia in amniotes, triggering appropriate respiratory responses for homeostasis (Nurse and Piskuric, 2013; Nurse, 2014; López-Barneo et al, 2016)
Since glomus cells produce dopamine and glial cell line-derived neurotrophic factor (GDNF), which promotes the survival of dopaminergic neurons (Erickson et al, 2001), the carotid body is a potential source of patient-specific stem cells for Parkinson's disease therapy (Espejo et al, 1998; Luquin et al, 1999; Mínguez-Castellanos et al, 2007; López-Barneo et al, 2009)
The sensitivity of neonatal adrenal chromaffin cells to both hypoxia (Comline and Silver, 1966; Cheung, 1989, 1990; Seidler and Slotkin, 1985, 1986; Thompson et al, 1997; García-Fernández et al, 2007; Levitsky and López-Barneo, 2009; López-Barneo et al, 2016) and hypercapnia (Muñoz-Cabello et al, 2005) led us to test the hypothesis that similar mechanisms underlie glomus cell and adrenal chromaffin cell development

Summary

Introduction

The carotid body is the primary site for monitoring arterial blood hypoxia (low O2 partial pressure) and hypercapnia (high CO2 partial pressure) in amniotes, triggering appropriate respiratory responses for homeostasis (Nurse and Piskuric, 2013; Nurse, 2014; López-Barneo et al, 2016). This small, highly vascularised chemosensory organ is entirely neural crest-derived, as shown by quail-chick grafting experiments in birds (Le Douarin et al, 1972; Pearse et al, 1973) and genetic lineage tracing in mice (Pardal et al, 2007). Since glomus cells produce dopamine and glial cell line-derived neurotrophic factor (GDNF), which promotes the survival of dopaminergic neurons (Erickson et al, 2001), the carotid body is a potential source of patient-specific stem cells for Parkinson's disease therapy (Espejo et al, 1998; Luquin et al, 1999; Mínguez-Castellanos et al, 2007; López-Barneo et al, 2009)

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Discussion

Conclusion