Document Detail

Fetal and postnatal lung defects reveal a novel and required role for Fgf8 in lung development.
MedLine Citation:
PMID:  20727874     Owner:  NLM     Status:  MEDLINE    
The fibroblast growth factor, FGF8, has been shown to be essential for vertebrate cardiovascular, craniofacial, brain and limb development. Here we report that Fgf8 function is required for normal progression through the late fetal stages of lung development that culminate in alveolar formation. Budding, lobation and branching morphogenesis are unaffected in early stage Fgf8 hypomorphic and conditional mutant lungs. Excess proliferation during fetal development disrupts distal airspace formation, mesenchymal and vascular remodeling, and Type I epithelial cell differentiation resulting in postnatal respiratory failure and death. Our findings reveal a previously unknown, critical role for Fgf8 function in fetal lung development and suggest that this factor may also contribute to postnatal alveologenesis. Given the high number of premature infants with alveolar dysgenesis and lung dysplasia, and the accumulating evidence that short-term benefits of available therapies may be outweighed by long-term detrimental effects on postnatal alveologenesis, the therapeutic implications of identifying a factor or pathway that can be targeted to stimulate normal alveolar development are profound.
Shibin Yu; Bryan Poe; Margaret Schwarz; Sarah A Elliot; Kurt H Albertine; Stephen Fenton; Vidu Garg; Anne M Moon
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-19
Journal Detail:
Title:  Developmental biology     Volume:  347     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-05     Completed Date:  2010-11-26     Revised Date:  2012-03-23    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  92-108     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Department of Pediatrics, University of Utah, Salt Lake City, UT 84112, USA.
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MeSH Terms
Animals, Newborn
Cell Differentiation
Cell Proliferation
Embryo, Mammalian / metabolism
Epithelium / metabolism,  pathology
Fetus / embryology*,  metabolism*
Fibroblast Growth Factor 8 / deficiency,  genetics,  metabolism*
Gene Expression Regulation, Developmental
Integrases / metabolism
Lung / abnormalities,  blood supply,  embryology*,  growth & development*
Mesoderm / metabolism,  pathology
Mutation / genetics
Grant Support
HL-60061/HL/NHLBI NIH HHS; HL-75764/HL/NHLBI NIH HHS; R01 HD044157-08/HD/NICHD NIH HHS; R01 HD044157-09/HD/NICHD NIH HHS; R01 HD044157-10/HD/NICHD NIH HHS; R01 HD044157-11/HD/NICHD NIH HHS
Reg. No./Substance:
0/Fgf8 protein, mouse; 148997-75-5/Fibroblast Growth Factor 8; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases

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

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