February 1, 2021;
Xenopus epidermal and endodermal epithelia as models for mucociliary epithelial evolution, disease, and metaplasia.
The Xenopus embryonic epidermis
is a powerful model to study mucociliary biology, development, and disease. Particularly, the Xenopus system is being used to elucidate signaling pathways, transcription factor functions, and morphogenetic mechanisms regulating cell fate specification, differentiation and cell function. Thereby, Xenopus research has provided significant insights into potential underlying molecular mechanisms for ciliopathies and chronic airway diseases. Recent studies have also established the embryonic epidermis
as a model for mucociliary epithelial remodeling, multiciliated cell trans-differentiation, cilia
loss, and mucus secretion. Additionally, the tadpole foregut epithelium
is lined by a mucociliary epithelium
, which shows remarkable features resembling mammalian airway epithelia, including its endodermal origin and a variable cell type composition along the proximal
axis. This review aims to summarize the advantages of the Xenopus epidermis
for mucociliary epithelial biology and disease modeling. Furthermore, the potential of the foregut epithelium
as novel mucociliary model system is being highlighted. Additional perspectives are presented on how to expand the range of diseases that can be modeled in the frog system, including proton pump inhibitor-associated pneumonia as well as metaplasia in epithelial cells of the airway and the gastroesophageal region.
Disease Ontology terms:
idiopathic pulmonary fibrosis
PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; COPD
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Development, function and remodeling of the Xenopus mucociliary epidermis. Schematic representation of key processes in life of the Xenopus embryonic mucociliary epidermis, from its specification to remodeling and loss of multiciliated cells. st., developmental stage; ECM, extracellular matrix; cell types are color‐coded, and a legend is given in the lower‐right corner of the figure. Please see text for details.
Morphology of the mucociliary epidermis and its cell types. (a–e) Scanning electron micrographs of the Xenopus epidermis during key stages of development and remodeling. Cell types are indicated. MCC, multiciliated cell; ISC, ionocyte; SSC, small secretory cell; goblet, mucus secreting goblet‐like cell. (a) Stage (st.) 25, (b) st. 30, (c) st. 40, (d) st. 41/42, and (e) st. 47/48. (f) Scanning electron micrograph of a mature Xenopus neuromast of the lateral line organ at st. 45/46. (g) MCC with shedding morphology at st. 41. (h) MCC with trans‐differentiation morphology at st. 45
The Xenopus foregut mucociliary epithelium. (a–d) Confocal micrographs of immunostained inner epithelial lining of the Xenopus stage (st.) 45 esophagus, stomach and anterior small intestine (smi). Multiciliated cells are stained for acetylated‐α‐tubulin (Ac.‐α‐tubulin, blue), mucus secretory cells are stained for mucins (PNA, magenta), and cell borders are stained with Phalloidin (actin, green). Magnified areas depicted in (b–d) are indicated by yellow boxes in (a). (e) Mucociliary marker gene expression revealed by in situ hybridization on isolated st. 45 guts. Panc, pancreas; stom, stomach. Image in (a) was reconstructed from multiple individual images
Ciliation of the Xenopus stomach during metamorphosis. (a–f) Confocal micrographs of cryosectioned and immunostained Xenopus stomach samples at (a) stage (st.) 51, (b) st. 56, (c) st. 61, and (d) st. 65 reveal ciliation of the stomach lining throughout metamorphosis. (e,f) Magnified views on tips of gastric folds at (e) st. 63 and (f) st. 65. Samples were stained for acetylated‐α‐tubulin (Ac.‐α‐tubulin, red), cell borders/the epithelium are stained with Phalloidin (actin, green), and nuclei were stained with DAPI (blue)
Analysis of ciliation in adult Xenopus tissues. (a–d) Confocal micrographs of immunostained adult Xenopus tissues. (a–d) Micrographs of (a,b) adult stomach samples, (c) the adult trachea, and (d) the adult lung stained for cilia (Ac.‐α‐tubulin, cyan), mucins (PNA, magenta), and F‐actin (actin, green) reveal lack of multiciliated cells (MCCs) in these tissues. (e) Micrographs of adult oviduct sample stained for cilia (Ac.‐α‐tubulin, magenta) and mucins (UEA, green) reveal a densely ciliated epithelium populated predominantly by MCCs with mucus secretory cells being interspersed. Images in (c–e) were reconstructed from multiple individual images