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Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors
Authors
Mori, MunemasaMahoney, John E.
Stupnikov, Maria R.
Paez-Cortez, Jesus R.
Szymaniak, Aleksander D.
Varelas, Xaralabos
Herrick, Dan B.
Schwob, James
Zhang, Hong
Cardoso, Wellington V.
UMass Chan Affiliations
Department of Cell and Developmental BiologyDocument Type
Journal ArticlePublication Date
2015-01-15Keywords
AnimalsBlotting, Western
Calcium-Binding Proteins
Cell Culture Techniques
Cell Differentiation
Epithelial Cells
Fluorescent Antibody Technique
Humans
Immunohistochemistry
In Situ Hybridization
Intercellular Signaling Peptides and Proteins
Lung
Membrane Proteins
Mice
Microscopy, Confocal
Real-Time Polymerase Chain Reaction
Receptors, Notch
Respiratory Mucosa
Signal Transduction
Species Specificity
Airway differentiation
Basal cells
COPD
Jagged
Lung regeneration
Notch
Progenitor cells
p63
Cell Biology
Cellular and Molecular Physiology
Developmental Biology
Metadata
Show full item recordAbstract
Basal cells are multipotent airway progenitors that generate distinct epithelial cell phenotypes crucial for homeostasis and repair of the conducting airways. Little is known about how these progenitor cells expand and transition to differentiation to form the pseudostratified airway epithelium in the developing and adult lung. Here, we show by genetic and pharmacological approaches that endogenous activation of Notch3 signaling selectively controls the pool of undifferentiated progenitors of upper airways available for differentiation. This mechanism depends on the availability of Jag1 and Jag2, and is key to generating a population of parabasal cells that later activates Notch1 and Notch2 for secretory-multiciliated cell fate selection. Disruption of this mechanism resulted in aberrant expansion of basal cells and altered pseudostratification. Analysis of human lungs showing similar abnormalities and decreased NOTCH3 expression in subjects with chronic obstructive pulmonary disease suggests an involvement of NOTCH3-dependent events in the pathogenesis of this condition.Source
Development. 2015 Jan 15;142(2):258-67. doi: 10.1242/dev.116855. Link to article on publisher's siteDOI
10.1242/dev.116855Permanent Link to this Item
http://hdl.handle.net/20.500.14038/26455PubMed ID
25564622Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1242/dev.116855