Heparan sulfate biosynthetic gene Ndst1 is required for FGF signaling in early lens development.

Abstract

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.

• Authors: Yi Pan, Andrea Woodbury, Jeffrey D Esko, Kay Grobe, Xin Zhang
• Journal: Development (Cambridge, England) (Development) Vol. 133 Issue 24 Pg. 4933-44 (Dec 2006) ISSN: 0950-1991 [Print] England
• PMID: 17107998 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Bone Morphogenetic Proteins
• Receptors, Fibroblast Growth Factor
• Wnt Proteins
• Fibroblast Growth Factors
• Heparitin Sulfate
• Sulfotransferases
• heparitin sulfotransferase

Topics

• Animals
• Bone Morphogenetic Proteins (metabolism)
• Down-Regulation
• Embryonic Development (genetics)
• Fibroblast Growth Factors (metabolism)
• Heparitin Sulfate (biosynthesis)
• Humans
• Lens, Crystalline (embryology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mutation
• Receptors, Fibroblast Growth Factor (metabolism)
• Signal Transduction
• Sulfotransferases (genetics)
• Wnt Proteins (metabolism)