QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 15 November 2006
doi: 10.1242/dev.02679

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.02679v1 133/24/4933    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pan, Y. Articles by Zhang, X. Search for Related Content PubMed PubMed Citation Articles by Pan, Y. Articles by Zhang, X. Social Bookmarking                         What's this?

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

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Yun, Y. Saijoh, K. E. Hirokawa, D. Kopinke, L. C. Murtaugh, E. S. Monuki, and E. M. Levine Lhx2 links the intrinsic and extrinsic factors that control optic cup formation Development, December 1, 2009; 136(23): 3895 - 3906. [Abstract] [Full Text] [PDF]

				R. I. Zuberi, X. N. Ge, S. Jiang, N. S. Bahaie, B. N. Kang, R. M. Hosseinkhani, E. M. Frenzel, M. M. Fuster, J. D. Esko, S. P. Rao, et al. Deficiency of Endothelial Heparan Sulfates Attenuates Allergic Airway Inflammation J. Immunol., September 15, 2009; 183(6): 3971 - 3979. [Abstract] [Full Text] [PDF]

				Z. Hu, C. Wang, Y. Xiao, N. Sheng, Y. Chen, Y. Xu, L. Zhang, W. Mo, N. Jing, and G. Hu NDST1-dependent heparan sulfate regulates BMP signaling and internalization in lung development J. Cell Sci., April 15, 2009; 122(8): 1145 - 1154. [Abstract] [Full Text] [PDF]

				S. Nadanaka and H. Kitagawa Heparan Sulphate Biosynthesis and Disease J. Biochem., July 1, 2008; 144(1): 7 - 14. [Abstract] [Full Text] [PDF]

				S. R. Pallerla, R. Lawrence, L. Lewejohann, Y. Pan, T. Fischer, U. Schlomann, X. Zhang, J. D. Esko, and K. Grobe Altered Heparan Sulfate Structure in Mice with Deleted NDST3 Gene Function J. Biol. Chem., June 13, 2008; 283(24): 16885 - 16894. [Abstract] [Full Text] [PDF]

				Y. Pan, C. Carbe, A. Powers, E. E. Zhang, J. D. Esko, K. Grobe, G.-S. Feng, and X. Zhang Bud specific N-sulfation of heparan sulfate regulates Shp2-dependent FGF signaling during lacrimal gland induction Development, January 15, 2008; 135(2): 301 - 310. [Abstract] [Full Text] [PDF]

				D. R. Newman, E. Walsh, K. B. C. Apparao, and P. L. Sannes Fibroblast growth factor-binding protein and N-deacetylase/N-sulfotransferase-1 expression in type II cells is modulated by heparin and extracellular matrix Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1314 - L1320. [Abstract] [Full Text] [PDF]

				F. M.D. Tholozan, C. Gribbon, Z. Li, M. W. Goldberg, A. R. Prescott, N. McKie, and R. A. Quinlan FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability Mol. Biol. Cell, November 1, 2007; 18(11): 4222 - 4231. [Abstract] [Full Text] [PDF]

				T. Kobayashi, H. Habuchi, K. Tamura, H. Ide, and K. Kimata Essential Role of Heparan Sulfate 2-O-Sulfotransferase in Chick Limb Bud Patterning and Development J. Biol. Chem., July 6, 2007; 282(27): 19589 - 19597. [Abstract] [Full Text] [PDF]

				M. M. Fuster, L. Wang, J. Castagnola, L. Sikora, K. Reddi, P. H.A. Lee, K. A. Radek, M. Schuksz, J. R. Bishop, R. L. Gallo, et al. Genetic alteration of endothelial heparan sulfate selectively inhibits tumor angiogenesis J. Cell Biol., May 7, 2007; 177(3): 539 - 549. [Abstract] [Full Text] [PDF]