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X. Zhang, Y. Pan, A. Woodbury, J.D. Esko, K. Grobe; Ndst1 is Required for FGF Signaling in Early Lens Development . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1097.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have implicated multiple signaling molecules, including bone morphogenic proteins (BMP) and fibroblast growth factors (FGF), in early lens development. However, regulation of these morphogen is still largely unknown. As essential components of major signaling pathways, heparan sulfate is known to participate in both morphogen transport and morphogen–receptor interaction. In this study, we investigate the role of the heparan sulfate biosynthetic gene Ndst1 in controling lens development.
The lens development in Ndst1 mutant embryos are analyzed by RNA in situ hybridization and immunohistochemistry.
We demonstrate that inactivation of the heparan sulfate biosynthetic gene Ndst1 results in early lens invagination defects, leading to severe lens hypoplasia or anophthalmia. Although Pax6 and Six3 are not affected, AP2α, Pitx3, Prox1 and αA crystallin expressions are disrupted in the mutant lens. We show that the Ndst1 mutants are not defective in BMP or Wnt signaling. Instead, these embryos exhibit reduced sulfation level of heparan sulfate, and diminished binding to FGF ligand or FGF/FGF receptor complex. Consistent with disruption of FGF signaling, expressions of phospho–ERK and ERM expression are also downregulated in Ndst1 mutant lens.
These results establish the important role of Ndst1 function in FGF signaling during lens development.
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