Molecular identity, anatomy, gene expression and function of neural crest vs. placode-derived nociceptors in the lower airways

Taylor‐Clark, Thomas E.

doi:10.1016/j.neulet.2020.135505

Cited by 12 publications

(15 citation statements)

References 165 publications

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“…Critically, studies have identified biochemical and genetic markers of airway sensory subsets that, when activated, evoke specific physiological responses ( Ricco et al, 1996 ; Ho et al, 2001 ; Undem et al, 2004 ; Kubin et al, 2006 ; Nassenstein et al, 2010 ; Lieu et al, 2011 ; Chang et al, 2015 ; Nonomura et al, 2017 ; Wang et al, 2017 ; Mazzone et al, 2020 ; Taylor-Clark, 2021 ). Lung sensory nerves have been broadly characterized into two groups: (1) myelinated fast conducting Aβ fibers that express the mechanosensitive Piezo2 channel and are activated by physiologically-relevant mechanical forces (inflation and deflation).…”

Section: Introductionmentioning

confidence: 99%

“…The vagal ganglion is actually comprised of two distinct ganglia (nodose and jugular), whose neuronal populations are derived from distinct embryological sources (placodes and neural crest, respectively; Taylor-Clark, 2021 ). Embryological origin defines gene expression, with selective expression of the transcription factor phox2b, the ion channels P2X 2 and 5HT 3 , and the neurotrophin receptor TRKB in nodose neurons, and selective expression of the signaling molecule Wnt1, the transcription factor Prdm12 and the neurotrophin receptor TRKA in jugular neurons ( Undem et al, 2004 ; Chuaychoo et al, 2005 ; Kwong et al, 2008 ; Nassenstein et al, 2010 ; Lieu et al, 2011 ; Nonomura et al, 2017 ; Kupari et al, 2019 ; Mazzone et al, 2020 ; Kim et al, 2020a , b ).…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, embryological origin also determines physiological function ( Taylor-Clark, 2021 ), e.g., jugular C fiber activation evokes cough and tachykinin-dependent neurogenic bronchospasm, whereas nodose C fiber activation decreases cough reflex sensitivity and fails to induce neurogenic bronchospasm ( Ellis and Undem, 1994 ; Muroi et al, 2013 ; Chou et al, 2018 ). However, heterogeneity in other reflex responses is not so easily explained: in anesthetized guinea pigs, inhalation of capsaicin causes tachypnea, whereas application of capsaicin to the trachea causes bradypnea and intravenous capsaicin causes tachypnea followed by bradypnea ( Chou et al, 2008 ).…”

Section: Introductionmentioning

confidence: 99%

“…Despite extensive characterization of the electrophysiological properties of airway afferent subsets, there is a gap in our understanding of their innervation patterns and how this impacts their sensitivity to physiological and pathophysiological stimuli. Immunohistochemistry (IHC) of lung afferents has yielded conflicting data ( Taylor-Clark, 2021 ) and is hampered by a lack of selective markers and the difficulty in labeling varicosities. Recently, genetically-defined afferents have been identified in the lung using cre-lox reporter systems ( Nonomura et al, 2017 ; Su et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Mapping of the Sensory Innervation of the Mouse Lung by Specific Vagal and Dorsal Root Ganglion Neuronal Subsets

Kim

Patil

Hadley

et al. 2022

eNeuro

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The airways are densely innervated by sensory afferent nerves, whose activation regulates respiration and triggers defensive reflexes (e.g., cough, bronchospasm). Airway innervation is heterogeneous, and distinct afferent subsets have distinct functional responses. However, little is known of the innervation patterns of subsets within the lung. A neuroanatomical map is critical for understanding afferent activation under physiological and pathophysiological conditions. Here, we quantified the innervation of the mouse lung by vagal and dorsal root ganglion (DRG) sensory subsets defined by the expression of Pirt (all afferents), 5HT 3 (vagal nodose afferents), Tac1 (tachykinergic afferents), and transient receptor potential vanilloid 1 channel (TRPV1; defensive/nociceptive afferents) using Cre-mediated reporter expression. We found that vagal afferents innervate almost all conducting airways and project into the alveolar region, whereas DRG afferents only innervate large airways. Of the two vagal ganglia, only nodose afferents project into the alveolar region, but both nodose and jugular afferents innervate conducting airways throughout the lung. Many afferents that project into the alveolar region express TRPV1. Few DRG afferents expressed TRPV1. Approximately 25% of blood vessels were innervated by vagal afferents (many were Tac1+). Approximately 10% of blood vessels had DRG afferents (some were Tac1+), but this was restricted to large vessels. Lastly, innervation of neuroepithelial bodies (NEBs) correlated with the cell number within the bodies. In conclusion, functionally distinct sensory subsets have distinct innervation patterns within the conducting airways, alveoli and blood vessels. Physiologic (e.g., stretch) and pathophysiological (e.g., inflammation, edema) stimuli likely vary throughout these regions. Our data provide a neuroanatomical basis for understanding afferent responses in vivo .

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mapping of the Sensory Innervation of the Mouse Lung by Specific Vagal and Dorsal Root Ganglion Neuronal Subsets

Kim

Patil

Hadley

et al. 2022

eNeuro

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“…Growing evidence demonstrates that these nerves serve critical functions. Vagus nerves that innervate the airways are essential for airway protective responses, including bronchospasm and cough reflex [6][7][8][9] . Recent studies have shown that a subset of vagal afferent neurons control breathing at birth and during homeostasis 10,11 .…”

Section: Introductionmentioning

confidence: 99%

Mapping the Central and Peripheral Projections of Lung Innervating Sensory Neurons

Y¹,

Barr²,

Jaquish³

et al. 2021

Preprint

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While best known as the gas exchange organ, the lung is also critical for sensing and responding to the aerosol environment in part through interaction with the nervous system. The rich diversity of lung innervating neurons remains poorly understood. Here, we interrogated the cell body location, projection pattern and targets of lung-innervating sensory neurons. Retrograde tracing from the lung labeled neurons primarily in the vagal ganglia, in a spatially distributed population expressing markers including Vglut2, Trpv1, Tac1, Calb1 or Piezo2. Centrally, they project to the nucleus of the solitary tract in the brainstem. Peripherally, they project along the branching airways and terminate on airway smooth muscles, vasculature including lymphatics, and selected alveoli. Notably, a discrete population of Calb1+ neurons preferentially innervate pulmonary neuroendocrine cells, a demonstrated airway sensor population. This comprehensive illustration of the properties of lung innervating sensory neurons serves as a foundation for understanding their function in lung.

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The pulmonary neuroepithelial body microenvironment represents an underestimated multimodal component in airway sensory pathways

Brouns

Adriaensen

Timmermans

2023

The Anatomical Record

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Exciting new imaging and molecular tools, combined with state‐of‐the‐art genetically modified mouse models, have recently boosted interest in pulmonary (vagal) sensory pathway investigations. In addition to the identification of diverse sensory neuronal subtypes, visualization of intrapulmonary projection patterns attracted renewed attention on morphologically identified sensory receptor end‐organs, such as the pulmonary neuroepithelial bodies (NEBs) that have been our area of expertise for the past four decades. The current review aims at providing an overview of the cellular and neuronal components of the pulmonary NEB microenvironment (NEB ME) in mice, underpinning the role of these complexly organized structures in the mechano‐ and chemosensory potential of airways and lungs. Interestingly, the pulmonary NEB ME additionally harbors different types of stem cells, and emerging evidence suggests that the signal transduction pathways that are active in the NEB ME during lung development and repair also determine the origin of small cell lung carcinoma. Although documented for many years that NEBs appear to be affected in several pulmonary diseases, the current intriguing knowledge on the NEB ME seems to encourage researchers that are new to the field to explore the possibility that these versatile sensor‐effector units may be involved in lung pathogenesis or pathobiology.

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Molecular identity, anatomy, gene expression and function of neural crest vs. placode-derived nociceptors in the lower airways

Cited by 12 publications

References 165 publications

Mapping of the Sensory Innervation of the Mouse Lung by Specific Vagal and Dorsal Root Ganglion Neuronal Subsets

Mapping of the Sensory Innervation of the Mouse Lung by Specific Vagal and Dorsal Root Ganglion Neuronal Subsets

Mapping the Central and Peripheral Projections of Lung Innervating Sensory Neurons

The pulmonary neuroepithelial body microenvironment represents an underestimated multimodal component in airway sensory pathways

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