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First published online 15 November 2006
doi: 10.1242/dev.02679
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1 Department of Medical and Molecular Genetics, Indiana University of Medicine,
Indianapolis, IN 46202, USA.
2 Department of Cellular and Molecular Medicine, Glycobiology Research and
Training Center, University of California, San Diego, 9500 Gilman Drive, La
Jolla, CA 92093, USA.
3 Department of General Zoology and Genetics, Westfälische
Wilhelms-Universität Münster, Schlossplatz 5, 48149 Münster,
Germany.
* Author for correspondence (e-mail: xz4{at}iupui.edu)
Accepted 4 October 2006
Multiple signaling molecules, including bone morphogenic proteins (BMP) and fibroblast growth factors (FGF), play important roles in early lens development. However, how these morphogens are regulated is still largely unknown. Heparan sulfate participates in both morphogen transport and morphogen-receptor interaction. In this study, we demonstrate that inactivation of the heparan sulfate biosynthetic gene Ndst1 resulted in invagination defects of the early lens and in the disruption of lens-determination gene expression, leading to severe lens hypoplasia or anophthalmia. Ndst1 mutants exhibited reduced sulfation of heparan sulfate, but both BMP- and Wnt-signaling remained unchanged. Instead, these embryos showed diminished binding of a subset of FGF proteins to FGF receptors. Consistent with disruption of FGF signaling, expression of phospho-Erk and ERM were also downregulated in Ndst1-mutant lenses. Taken together, these results establish an important role of Ndst1 function in FGF signaling during lens development.
Key words: Ndst, HSPG, BMP, Wnt, FGF, Erk, Signaling, Lens, Induction, Mouse
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