Document Detail


Fibroblast growth factor 10 plays a causative role in the tracheal cartilage defects in a mouse model of Apert syndrome.
MedLine Citation:
PMID:  19581825     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients with Apert syndrome (AS) display a wide range of congenital malformations including tracheal stenosis, which is a disease characterized by a uniform cartilaginous sleeve in place of a normally ribbed cartilagenous trachea. We have studied the cellular and molecular basis of this phenotype in a mouse model of AS (Fgfr2c(+/Delta) mice), which shows ectopic expression of Fgfr2b in mesenchymal tissues. Here we report that tracheal stenosis is associated with increased proliferation of mesenchymal cells, where the expression of Fgf10 and its upstream regulators Tbx4 and Tbx5 are abnormally elevated. We show that Fgf10 has a critical inductive role in tracheal stenosis, as genetic knockdown of Fgf10 in Fgfr2c(+/Delta) mice rescues this phenotype. These novel findings demonstrate a regulatory role for Fgf10 in tracheal development and shed more light on the underlying cause of tracheal defects in AS.
Authors:
Caterina Tiozzo; Stijn De Langhe; Gianni Carraro; Denise Al Alam; Andre Nagy; Clarence Wigfall; Mohammad K Hajihosseini; David Warburton; Parviz Minoo; Saverio Bellusci
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric research     Volume:  66     ISSN:  1530-0447     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-12-17     Completed Date:  2010-02-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  386-90     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Women's and Children's Hospital, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.
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MeSH Terms
Descriptor/Qualifier:
Acrocephalosyndactylia / metabolism,  pathology*
Animals
Body Patterning
Cartilage / abnormalities*
Embryo, Mammalian / anatomy & histology,  physiology
Fibroblast Growth Factor 10 / genetics,  metabolism*
Humans
Mice
Mice, Transgenic
Phenotype
Receptor, Fibroblast Growth Factor, Type 2 / genetics,  metabolism
Signal Transduction / physiology
T-Box Domain Proteins / genetics,  metabolism
Trachea / anatomy & histology*
Grant Support
ID/Acronym/Agency:
1R01HL086322/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibroblast Growth Factor 10; 0/T-Box Domain Proteins; 0/Tbx4 protein, mouse; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 2

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


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