Document Detail


Neuroepithelial body microenvironment is a niche for a distinct subset of Clara-like precursors in the developing airways.
MedLine Citation:
PMID:  22797898     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Clara cells of mammalian airways have multiple functions and are morphologically heterogeneous. Although Notch signaling is essential for the development of these cells, it is unclear how Notch influences Clara cell specification and if diversity is established among Clara cell precursors. Here we identify expression of the secretoglobin Scgb3a2 and Notch activation as early events in a program of secretory cell fate determination in developing murine airways. We show that Scgb3a2 expression in vivo is Notch-dependent at early stages and ectopically induced by constitutive Notch1 activation, and also that in vitro Notch signaling together with the pan-airway transcription factor Ttf1 (Nkx2.1) synergistically regulate secretoglobin gene transcription. Furthermore, we identified a subpopulation of secretory precursors juxtaposed to presumptive neuroepithelial bodies (NEBs), distinguished by their strong Scgb3a2 and uroplakin 3a (Upk3a) signals and reduced Ccsp (Scgb1a1) expression. Genetic ablation of Ascl1 prevented NEB formation and selectively interfered with the formation of this subpopulation of cells. Lineage labeling of Upk3a-expressing cells during development showed that these cells remain largely uncommitted during embryonic development and contribute to Clara and ciliated cells in the adult lung. Together, our findings suggest a role for Notch in the induction of a Clara cell-specific program of gene expression, and reveals that the NEB microenvironment in the developing airways is a niche for a distinct subset of Clara-like precursors.
Authors:
Arjun Guha; Michelle Vasconcelos; Yan Cai; Mitsuhiro Yoneda; Anne Hinds; Jun Qian; Guihua Li; Lauren Dickel; Jane E Johnson; Shioko Kimura; Jinjin Guo; Jill McMahon; Andrew P McMahon; Wellington V Cardoso
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-13
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-08-01     Completed Date:  2012-10-26     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12592-7     Citation Subset:  IM    
Affiliation:
Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. aguha@bu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Female
Gene Expression Regulation, Developmental / physiology
Mice
Mice, Knockout
Neuroepithelial Bodies / cytology,  metabolism*
Nuclear Proteins / genetics,  metabolism
Receptors, Notch / genetics,  metabolism
Respiratory System / cytology,  embryology*
Secretoglobins / biosynthesis,  genetics
Stem Cell Niche / physiology*
Stem Cells / cytology,  metabolism*
Transcription Factors / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
P01 HL47049/HL/NHLBI NIH HHS; R01 HL105971/HL/NHLBI NIH HHS; R01 HL105971/HL/NHLBI NIH HHS; R01 NS032817/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Nuclear Proteins; 0/Receptors, Notch; 0/Scgb3a2 protein, mouse; 0/Secretoglobins; 0/Transcription Factors; 0/thyroid nuclear factor 1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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