Document Detail


Foxm1 transcription factor is critical for proliferation and differentiation of Clara cells during development of conducting airways.
MedLine Citation:
PMID:  22885335     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Respiratory epithelial cells are derived from cell progenitors in the foregut endoderm that subsequently differentiate into the distinct cell types lining the conducting and alveolar regions of the lung. To identify transcriptional mechanisms regulating differentiation and maintenance of respiratory epithelial cells, we conditionally deleted Foxm1 transcription factor from the conducting airways of the developing mouse lung. Conditional deletion of Foxm1 from Clara cells, controlled by the Scgb1a1 promoter, dramatically altered airway structure and caused peribronchial fibrosis, resulting in airway hyperreactivity in adult mice. Deletion of Foxm1 inhibited proliferation of Clara cells and disrupted the normal patterning of epithelial cell differentiation in the bronchioles, causing squamous and goblet cell metaplasia, and the loss of Clara and ciliated cells. Surprisingly, conducting airways of Foxm1-deficient mice contained highly differentiated cuboidal type II epithelial cells that are normally restricted to the alveoli. Lineage tracing studies showed that the ectopic alveolar type II cells in Foxm1-deficient airways were derived from Clara cells. Deletion of Foxm1 inhibited Sox2 and Scgb1a1, both of which are critical for differentiation and function of Clara cells. In co-transfection experiments, Foxm1 directly bound to and induced transcriptional activity of Scgb1a1 and Sox2 promoters. Foxm1 is required for differentiation and maintenance of epithelial cells lining conducting airways.
Authors:
Vladimir Ustiyan; Susan E Wert; Machiko Ikegami; I-Ching Wang; Tanya V Kalin; Jeffrey A Whitsett; Vladimir V Kalinichenko
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-02
Journal Detail:
Title:  Developmental biology     Volume:  370     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-14     Completed Date:  2012-11-19     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  198-212     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Division of Pulmonary Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation*
Cell Proliferation*
Epithelial Cells / cytology
Forkhead Transcription Factors / genetics,  metabolism*
Gene Deletion
Lung / cytology,  growth & development
Mice
Pulmonary Alveoli / cytology
Respiratory System / cytology*,  growth & development*
SOXB1 Transcription Factors / metabolism
Transcriptome
Uteroglobin / metabolism
Grant Support
ID/Acronym/Agency:
CA142724/CA/NCI NIH HHS; HL095464/HL/NHLBI NIH HHS; HL84151/HL/NHLBI NIH HHS; R01 CA142724/CA/NCI NIH HHS; R01 HL084151/HL/NHLBI NIH HHS; R01 HL095464/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Forkhead Transcription Factors; 0/Foxm1 protein, mouse; 0/SOXB1 Transcription Factors; 0/Scgb1a1 protein, mouse; 0/Sox2 protein, mouse; 9060-09-7/Uteroglobin
Comments/Corrections

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