Jagged and Delta ligands control distinct events during airway progenitor cell differentiation

Abstract
Data availability
Article and author information
Metrics

Abstract

Notch signaling regulates cell fate selection during development in multiple organs including the lung. Previous studies on the role of Notch in the lung focused mostly on Notch pathway core components or receptor-specific functions. It is unclear, however, how individual (Dll1/Dll4/Jag1/Jag2) or families of ligands (Delta/Jagged) influence differentiation of airway epithelial progenitors. Using mouse genetic models we show major differences in Jag and Dll in regulation and establishment of cell fate. Jag ligands had a major impact in balancing distinct cell populations in conducting airways, but had no role in establishment of domains and cellular abundance in the neuroendocrine (NE) microenvironment. Surprisingly, Dll ligands were crucial in restricting cell fate and size of NE bodies and showed an overlapping role with Jag in differentiation of NE-associated secretory (club) cells. These mechanisms may potentially play a role in human conditions that result in aberrant NE differentiation, including NE hyperplasias and cancer.

Data availability

All data generated or analyzed have been included in the manuscript and supporting files. No databases have been generated in this study.

Article and author information

Author details

Maria R Stupnikov

Columbia Center for Human Development, Department of Medicine, Pulmonary Allergy Critical Care, Columbia University Medical Center, New York, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5349-5233
Ying Yang

Columbia Center for Human Development, Department of Medicine, Pulmonary Allergy Critical Care, Columbia University Medical Center, New York, United States

Competing interests
The authors declare that no competing interests exist.
Munemasa Mori

Columbia Center for Human Development, Department of Medicine, Pulmonary Allergy Critical Care, Columbia University Medical Center, New York, United States

Competing interests
The authors declare that no competing interests exist.
Jining Lu

Columbia Center for Human Development, Department of Medicine, Pulmonary Allergy Critical Care, Columbia University Medical Center, New York, United States

Competing interests
The authors declare that no competing interests exist.
Wellington V Cardoso

Columbia Center for Human Development, Department of Medicine, Pulmonary Allergy Critical Care, Columbia University Medical Center, New York, United States

For correspondence
wvc2104@cumc.columbia.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8868-9716

Funding

National Heart, Lung, and Blood Institute (R35-HL135834-01)

Wellington V Cardoso

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (AAAS0503) of Columbia University.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.