Document Detail


Defective FGF signaling causes coloboma formation and disrupts retinal neurogenesis.
MedLine Citation:
PMID:  23147794     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The optic fissure (OF) is a transient opening on the ventral side of the developing vertebrate eye that closes before nearly all retinal progenitor cell differentiation has occurred. Failure to close the OF results in coloboma, a congenital disease that is a major cause of childhood blindness. Although human genetic studies and animal models have linked a number of genes to coloboma, the cellular and molecular mechanisms driving the closure of the OF are still largely unclear. In this study, we used Cre-LoxP-mediated conditional removal of fibroblast growth factor (FGF) receptors, Fgfr1 and Fgfr2, from the developing optic cup (OC) to show that FGF signaling regulates the closing of the OF. Our molecular, cellular and transcriptome analyses of Fgfr1 and Fgfr2 double conditional knockout OCs suggest that FGF signaling controls the OF closure through modulation of retinal progenitor cell proliferation, fate specification and morphological changes. Furthermore, Fgfr1 and Fgfr2 double conditional mutant retinal progenitor cells fail to initiate retinal ganglion cell (RGC) genesis. Taken together, our mouse genetic studies reveal that FGF signaling is essential for OF morphogenesis and RGC development.
Authors:
Shuyi Chen; Hua Li; Karin Gaudenz; Ariel Paulson; Fengli Guo; Rhonda Trimble; Allison Peak; Christopher Seidel; Chuxia Deng; Yasuhide Furuta; Ting Xie
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-13
Journal Detail:
Title:  Cell research     Volume:  23     ISSN:  1748-7838     ISO Abbreviation:  Cell Res.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-04     Completed Date:  2013-08-13     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  9425763     Medline TA:  Cell Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  254-73     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Coloboma / metabolism*,  pathology
Fibroblast Growth Factors / metabolism*
Gene Expression Profiling
Mice
Mice, Knockout
Neurogenesis
Receptor, Fibroblast Growth Factor, Type 1 / deficiency,  genetics,  metabolism
Receptor, Fibroblast Growth Factor, Type 2 / deficiency,  genetics,  metabolism
Retina / cytology*
Retinal Ganglion Cells / cytology,  metabolism
Signal Transduction*
Stem Cells / cytology,  metabolism
Grant Support
ID/Acronym/Agency:
EY012128/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
62031-54-3/Fibroblast Growth Factors; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 1; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 2
Comments/Corrections

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