Document Detail

Genetic epistasis between heparan sulfate and FGF-Ras signaling controls lens development.
MedLine Citation:
PMID:  21536023     Owner:  NLM     Status:  MEDLINE    
Vertebrate lens development depends on a complex network of signaling molecules to coordinate cell proliferation, migration and differentiation. In this study, we have investigated the role of heparan sulfate in lens specific signaling by generating a conditional ablation of heparan sulfate modification genes, Ndst1 and Ndst2. In this mutant, N-sulfation of heparan sulfate was disrupted after the lens induction stage, resulting in reduced lens cell proliferation, increased cell death and defective lens fiber differentiation in later lens development. The loss of Ndst function also prevented the assembly of Fgf/Fgfr complexes on the lens cell surface and disrupted ERK signaling within the lens. We further demonstrated that Ndst mutation completely inhibited the FGF1 and Fgf3 overexpression phenotypes, but Kras reactivation was sufficient to reverse the Ndst deficient lens differentiation defect. The epistatic relationship between Ndst and FGF-Ras signaling demonstrates that FGF signaling is the predominant signaling pathway controlled by Ndst in lens development.
Xiuxia Qu; Kristina Hertzler; Yi Pan; Kay Grobe; Michael L Robinson; Xin Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-04-17
Journal Detail:
Title:  Developmental biology     Volume:  355     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-05-30     Completed Date:  2011-08-09     Revised Date:  2014-09-15    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12-20     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Amidohydrolases / genetics,  metabolism*
Cell Death
Cell Differentiation
Cell Proliferation
Epistasis, Genetic*
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
Fibroblast Growth Factors / genetics*
Heparitin Sulfate / genetics*
Lens, Crystalline / enzymology,  growth & development*
Mice, Transgenic
Receptors, Fibroblast Growth Factor / metabolism
Signal Transduction
Sulfotransferases / genetics,  metabolism*
ras Proteins / genetics*
Grant Support
EY012995/EY/NEI NIH HHS; EY017061/EY/NEI NIH HHS; R01 EY017061/EY/NEI NIH HHS; R01 EY017061-06/EY/NEI NIH HHS
Reg. No./Substance:
0/Receptors, Fibroblast Growth Factor; 62031-54-3/Fibroblast Growth Factors; 9050-30-0/Heparitin Sulfate; EC Signal-Regulated MAP Kinases; EC 2.8.2.-/Ndst2 protein, mouse; EC 2.8.2.-/Sulfotransferases; EC sulfotransferase; EC 3.5.-/Amidohydrolases; EC Proteins

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