کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2173708 1093742 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Genetic epistasis between heparan sulfate and FGF–Ras signaling controls lens development
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Genetic epistasis between heparan sulfate and FGF–Ras signaling controls lens development
چکیده انگلیسی

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.

Research highlights
► Ndst-mediated heparan sulfate modification is required for lens cell proliferation, survival and differentiation.
► Ndst mutation prevents FGF signaling induced lens fiber differentiation.
► Ras signaling can rescue Ndst mutant lens defects.
► FGF–Ras signaling is the main signaling pathway regulated by Ndst in lens development.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Developmental Biology - Volume 355, Issue 1, 1 July 2011, Pages 12–20
نویسندگان
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