Ontogeny of airway smooth muscle: structure, innervation, myogenesis and function in the fetal lung

Sparrow, Malcolm; Lamb, Jasmine

doi:10.1016/s1569-9048(03)00159-9

Cited by 63 publications

(46 citation statements)

References 31 publications

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“…Sagittal sections of the trachea show cell bodies of the intrinsic neurons located dorsally in association with the smooth muscle that connects the cartilage rings ( Figure 1F). The processes of these intrinsic neurons extend into the smooth muscle ( Figure 1F, inset), supporting the concept that they control the contractility of tracheal smooth muscle (34).…”

Section: Intrinsic Neurons In the Respiratory Tract Have Discrete Anasupporting

confidence: 70%

“…We show that intrinsic neurons are distributed asymmetrically in the trachea and primary bronchi, and that the number of neurons decreases along the proximal-distal axis of the pulmonary tree. Such a discrete anatomic distribution of intrinsic neurons likely correlates with the localization of target tissues of innervation, such as smooth muscle cells in the trachea and airways, and neuroendocrine cells, which are more abundant in the proximal lung (34)(35)(36). However, according to a recent study, vagal denervation disrupts a large majority of nerve fibers that innervate neuroendocrine cells, suggesting that intrinsic neurons contribute minimally to neuroendocrine innervation (37).…”

Section: Discussionmentioning

confidence: 99%

“…A small number of intrinsic neurons are found along the secondary and tertiary bronchi ( Figure 1H), with very few neurons in more distal region. Despite the paucity of intrinsic neurons in the distal lung, TuJ1 1 neural fibers are readily identifiable in the proximity of airway smooth muscle and neuroendocrine cells ( Figures 1I and 1J) (34)(35)(36)(37).…”

Section: Intrinsic Neurons In the Respiratory Tract Have Discrete Anamentioning

confidence: 99%

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Neural Crest Cell Origin and Signals for Intrinsic Neurogenesis in the Mammalian Respiratory Tract

Langsdorf

Radzikinas

Kroten

et al. 2011

Am J Respir Cell Mol Biol

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Our study investigates the innervation of the respiratory tract during mouse embryonic development, with a focus on the identification of cell origin and essential developmental signals for the resident, or intrinsic, neurons. Using lineage tracing, we show that these intrinsic neurons are exclusively derived from neural crest cells, and cluster to form ganglia that reside in the dorsal trachea and medial bronchi with diminishing frequency. Comparisons of intrinsic neurogenesis between wild-type, glial cell-derived neurotrophic factor (GDNF) 2/2 , neurturin 2/2 , and tyrosine kinase receptor Ret 2/2 embryos, in combination with lung organ cultures, identified that Ret signaling, redundantly activated by GDNF family members, is required for intrinsic neurogenesis in the trachea and primary bronchi. In contrast, Ret deficiency exerts no effect on the innervation of the rest of the respiratory tract, suggesting that innervation by neurons whose cell bodies are located outside of the lung (so-called extrinsic neurons) is independent of Ret signaling. Furthermore, although the trachea, the esophagus, and their intrinsic neurons share foregut endoderm and a neural crest cell origin, respectively, the signals required for their intrinsic neurogenesis are divergent. Together, our results not only establish the neural crest lineage of intrinsic neurons in the respiratory tract, but also identify regional differences in the abundance and developmental signals of intrinsic neurons along the respiratory tract and in the esophagus.

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Section: Intrinsic Neurons In the Respiratory Tract Have Discrete Anasupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Intrinsic Neurons In the Respiratory Tract Have Discrete Anamentioning

confidence: 99%

See 1 more Smart Citation

Neural Crest Cell Origin and Signals for Intrinsic Neurogenesis in the Mammalian Respiratory Tract

Langsdorf

Radzikinas

Kroten

et al. 2011

Am J Respir Cell Mol Biol

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“…Airway SM originates from various sources, including mesenchymal cells of the developing lung during formation of the bronchial tree (17)(18)(19)(20). During development, the airway SM is responsible for phasic contractility of the liquid-filled epithelial tubules and production of growth factors, both critical for normal lung growth (21,22).…”

Section: Introductionmentioning

confidence: 99%

Prenatal retinoid deficiency leads to airway hyperresponsiveness in adult mice

et al. 2014

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There is increasing evidence that vitamin A deficiency in utero correlates with abnormal airway smooth muscle (SM) function in postnatal life. The bioactive vitamin A metabolite retinoic acid (RA) is essential for formation of the lung primordium; however, little is known about the impact of early fetal RA deficiency on postnatal lung structure and function. Here, we provide evidence that during murine lung development, endogenous RA has a key role in restricting the airway SM differentiation program during airway formation. Using murine models of pharmacological, genetic, and dietary vitamin A/RA deficiency, we found that disruption of RA signaling during embryonic development consistently resulted in an altered airway SM phenotype with markedly increased expression of SM markers. The aberrant phenotype persisted postnatally regardless of the adult vitamin A status and manifested as structural changes in the bronchial SM and hyperresponsiveness of the airway without evidence of inflammation. Our data reveal a role for endogenous RA signaling in restricting SM differentiation and preventing precocious and excessive SM differentiation when airways are forming.

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“…Both in vivo and in organ culture, a previous study demonstrated the early pseudoglandular stage of the lung as a dynamic structure, with smooth muscle and neural tissue in a prime position to influence growth and development (6). During embryonic lung development, intrinsic nerve ganglia function to innervate the airway smooth muscle (7). NEBs are extensively innervated, and may act as sensory airway receptors (8).…”

mentioning

confidence: 99%

Multidirectional Differentiation of Achaete–Scute Homologue–1–Defined Progenitors in Lung Development and Injury Repair

Linnoila

2012

Am J Respir Cell Mol Biol

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Multiple cells contribute to the function of lungs. Pulmonary neuroendocrine cells (PNECs) are important for the regulation of breathing and carcinogenesis, although they represent only a small population of the airway lining. Achaete-Scute homologue-1 (Ascl1), a proneural basic helix-loop-helix transcription factor, is critical for the development of PNECs. We postulated that Ascl1-defined cells (ASDCs) may be progenitors, and traced their fate during development and injury repair. R26R-stop-lacZ (Rosa) reporter mice were crossed with Ascl1-Cre or Ascl1-CreERTM mice, in which the Ascl1 promoter drives the expression of Cre or inducible Cre recombinase, respectively. ASDCs and their descendants will be permanently labeled. The labeled cells were characterized by immunohistochemistry, using highly specific differentiation markers. Lineage studies revealed a population that proliferates before the pseudoglandular stage, and widely contributes to different compartments. When ASDCs were labeled on Embryonic Day 9.5, they gave rise to both airway and alveolar cells, but when labeled on Embryonic Day 11.5, they only gave rise to airway cells. In postnatal naphthalene injury, ASDCs contributed to regenerating Clara cells. In conclusion, Ascl1-defined cells in the lung represent a novel multipotent lineage, indicating a close relationship of neuroendocrine cells with other cell types.Keywords: Ascl1; lung; neuroendocrine; mouse; progenitor The murine respiratory system arises from the ventral foregut endoderm at around Embryonic Day (E) 9.5. The lung-bud epithelium invades the adjacent mesenchyme and starts branching to form a tree-like structure. The epithelium begins to differentiate during the pseudoglandular stage (E9.5-E16.5) (1). Multiple cell types contribute to both the structure and function of the lung. In the alveoli, Type II pneumocytes (AT2 cells) secrete surfactant, whereas Type I cells are responsible for gas exchange. In the airways, nonciliated secretory (Clara) cells have metabolic, anti-inflammatory, and anti-neoplastic properties, whereas ciliated cells eliminate excess mucus and harmful particles. In addition, the airway lining contains rare but important pulmonary neuroendocrine cells (PNECs) that may regulate breathing and contribute to carcinogenesis (2-4). PNECs occur as either solitary cells or clusters called neuroepithelial bodies (NEBs) (5). In developing lungs, PNECs begin to differentiate before other cells, but their histogenesis has remained elusive.Lung development is a complex process that requires mutual interactions between the mesoderm-derived mesenchyme and endoderm-derived epithelium. Both in vivo and in organ culture, a previous study demonstrated the early pseudoglandular stage of the lung as a dynamic structure, with smooth muscle and neural tissue in a prime position to influence growth and development (6). During embryonic lung development, intrinsic nerve ganglia function to innervate the airway smooth muscle (7). NEBs are extensively innervated, and may act as sensory airwa...

show abstract

Ontogeny of airway smooth muscle: structure, innervation, myogenesis and function in the fetal lung

Cited by 63 publications

References 31 publications

Neural Crest Cell Origin and Signals for Intrinsic Neurogenesis in the Mammalian Respiratory Tract

Neural Crest Cell Origin and Signals for Intrinsic Neurogenesis in the Mammalian Respiratory Tract

Prenatal retinoid deficiency leads to airway hyperresponsiveness in adult mice

Multidirectional Differentiation of Achaete–Scute Homologue–1–Defined Progenitors in Lung Development and Injury Repair

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