The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Notch signaling controls the balance of ciliated and secretory cell fates in developing airways
Open accessAbstract
Although there is accumulated evidence of a role for Notch in the developing lung, it is still unclear how disruption of Notch signaling affects lung progenitor cell fate and differentiation events in the airway epithelium. To address this issue, we inactivated Notch signaling conditionally in the endoderm using a Shh-Cre deleter mouse line and mice carrying floxed alleles of the Pofut1 gene, which encodes an O-fucosyltransferase essential for Notch-ligand binding. We also took the same conditional approach to inactivate expression of Rbpjk, which encodes the transcriptional effector of canonical Notch signaling. Strikingly, these mutants showed an almost identical lung phenotype characterized by an absence of secretory Clara cells without evidence of cell death, and showed airways populated essentially by ciliated cells, with an increase in neuroendocrine cells. This phenotype could be further replicated in cultured wild-type lungs by disrupting Notch signaling with a gamma-secretase inhibitor. Our data suggest that Notch acts when commitment to a ciliated or non-ciliated cell fate occurs in proximal progenitors, silencing the ciliated program in the cells that will continue to expand and differentiate into secretory cells. This mechanism may be crucial to define the balance of differentiated cell profiles in different generations of the developing airways. It might also be relevant to mediate the metaplastic changes in the respiratory epithelium that occur in pathological conditions, such as asthma and chronic obstructive pulmonary disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Protein O -fucosyltransferase 1 is an essential component of Notch signaling pathways
Shi, S., & Stanley, P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0831126100 · Cited by 381
Cited by
A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte
Plasschaert, L. W., Žilionis, R., Choo-Wing, R., Savova, V., Knehr, J., Roma, G., Klein, A. M., & Jaffe, A. B. (2018) · Nature · doi:10.1038/s41586-018-0394-6 · Cited by 1,047
Preparing for the First Breath: Genetic and Cellular Mechanisms in Lung Development
Morrisey, E. E., & Hogan, B. L. M. (2010) · Developmental Cell · doi:10.1016/j.devcel.2009.12.010 · Cited by 964
Hogan, B. L. M., Barkauskas, C. E., Chapman, H. A., Epstein, J. A., Jain, R., Hsia, C. C. W., Niklason, L., Calle, E., Le, A., Randell, S. H., et al. (2014) · Cell Stem Cell · doi:10.1016/j.stem.2014.07.012 · Cited by 876
The development and functions of multiciliated epithelia
Spassky, N., & Meunier, A. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.21 · Cited by 389
Ruiz García, S., Deprez, M., Lebrigand, K., Cavard, A., Paquet, A., Arguel, M.-J., Magnone, V., Truchi, M., Caballero, I., Leroy, S., et al. (2019) · Development · doi:10.1242/dev.177428 · Cited by 297
miR-34/449 miRNAs are required for motile ciliogenesis by repressing CP110
Song, R., Walentek, P., Sponer, N., Klimke, A., Lee, J. S., Dixon, G., Harland, R., Wan, Y., Lishko, P., Lize, M., et al. (2014) · Nature · doi:10.1038/nature13413 · Cited by 228
Molecular pathways and therapeutic targets in lung cancer
Shtivelman, E., Hensing, T., Simon, G. R., Dennis, P. A., Otterson, G. A., Bueno, R., & Salgia, R. (2014) · Oncotarget · doi:10.18632/oncotarget.1891 · Cited by 220
“Notch signaling is required for the cell- fate decision between ciliated and non-ciliated secretory epithelium in developing lung [213].”
BackgroundMotile cilia and airway disease
Legendre, M., Zaragosi, L.-E., & Mitchison, H. M. (2021) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2020.11.007 · Cited by 175
Multiciliated Cells in Animals
Meunier, A., & Azimzadeh, J. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028233 · Cited by 117
Lung cancer stem cell markers as therapeutic targets: An update on signaling pathways and therapies
Zheng, Y., Wang, L., Yin, L., Yao, Z., Tong, R., Xue, J., & Lu, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.873994 · Cited by 97
Emerging Roles of Airway Epithelial Cells in Idiopathic Pulmonary Fibrosis
Chakraborty, A., Mastalerz, M., Ansari, M., Schiller, H. B., & Staab-Weijnitz, C. A. (2022) · Cells · doi:10.3390/cells11061050 · Cited by 68
Cilia in cell signaling and human disorders
Duldulao, N. A., Li, J., & Sun, Z. (2010) · Protein & Cell · doi:10.1007/s13238-010-0098-7 · Cited by 13
Metadata
- Authors
- Tsao, P.-N., Vasconcelos, M., Izvolsky, K. I., Qian, J., Lu, J., & Cardoso, W. V.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2009-07-01
- Volume
- 136
- Issue
- 13
- Pages
- 2297-2307
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2149454565
- Cited by
- 380
- References
- 1
- FWCI
- 7.68
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
