| Genetic epistasis between heparan sulfate and FGF-Ras signaling controls lens development. | |
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MedLine Citation:
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PMID: 21536023 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Xiuxia Qu; Kristina Hertzler; Yi Pan; Kay Grobe; Michael L Robinson; Xin Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-04-17 |
Journal Detail:
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Title: Developmental biology Volume: 355 ISSN: 1095-564X ISO Abbreviation: Dev. Biol. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-05-30 Completed Date: 2011-08-09 Revised Date: 2012-09-20 |
Medline Journal Info:
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Nlm Unique ID: 0372762 Medline TA: Dev Biol Country: United States |
Other Details:
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Languages: eng Pagination: 12-20 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amidohydrolases
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genetics,
metabolism* Animals 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 Mice, Transgenic Mutation Receptors, Fibroblast Growth Factor / metabolism Signal Transduction Sulfotransferases / genetics, metabolism* ras Proteins / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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EY012995/EY/NEI NIH HHS; EY017061/EY/NEI NIH HHS; R01 EY017061-06/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Fibroblast Growth Factor; 62031-54-3/Fibroblast Growth Factors; 9050-30-0/Heparitin Sulfate; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.8.2.-/Ndst2 protein, mouse; EC 2.8.2.-/Sulfotransferases; EC 2.8.2.8/heparitin sulfotransferase; EC 3.5.-/Amidohydrolases; EC 3.6.5.2/ras Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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