Vascular development in the retina and inner ear: Control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair

Qiang Xu, Yanshu Wang, Alain Dabdoub, Philip M. Smallwood, John Williams, Chad Woods, Matthew W. Kelley, Li Jiang, William Tasman, Kang Zhang, Jeremy Nathans

Research output: Contribution to journalArticle

Abstract

Incomplete retinal vascularization occurs in both Norrie disease and familial exudative vitreoretinopathy (FEVR). Norrin, the protein product of the Norrie disease gene, is a secreted protein of unknown biochemical function. One form of FEVR is caused by defects in Frizzled-4 (Fz4), a presumptive Wnt receptor. We show here that Norrin and Fz4 function as a ligand-receptor pair based on (1) the similarity in vascular phenotypes caused by Norrin and Fz4 mutations in humans and mice, (2) the specificity and high affinity of Norrin-Fz4 binding, (3) the high efficiency with which Norrin induces Fz4- and Lrp-dependent activation of the classical Wnt pathway, and (4) the signaling defects displayed by disease-associated variants of Norrin and Fz4. These data define a Norrin-Fz4 signaling system that plays a central role in vascular development in the eye and ear, and they indicate that ligands unrelated to Wnts can act through Fz receptors.

Original languageEnglish (US)
Pages (from-to)883-895
Number of pages13
JournalCell
Volume116
Issue number6
DOIs
StatePublished - Mar 19 2004

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Inner Ear
Blood Vessels
Retina
Wnt Receptors
Ligands
Wnt Signaling Pathway
Ear
Defects
Proteins
Phenotype
Mutation
Genes
Chemical activation
Familial Exudative Vitreoretinopathy
Norrie disease

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Vascular development in the retina and inner ear : Control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. / Xu, Qiang; Wang, Yanshu; Dabdoub, Alain; Smallwood, Philip M.; Williams, John; Woods, Chad; Kelley, Matthew W.; Jiang, Li; Tasman, William; Zhang, Kang; Nathans, Jeremy.

In: Cell, Vol. 116, No. 6, 19.03.2004, p. 883-895.

Research output: Contribution to journalArticle

Xu, Q, Wang, Y, Dabdoub, A, Smallwood, PM, Williams, J, Woods, C, Kelley, MW, Jiang, L, Tasman, W, Zhang, K & Nathans, J 2004, 'Vascular development in the retina and inner ear: Control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair', Cell, vol. 116, no. 6, pp. 883-895. https://doi.org/10.1016/S0092-8674(04)00216-8
Xu, Qiang ; Wang, Yanshu ; Dabdoub, Alain ; Smallwood, Philip M. ; Williams, John ; Woods, Chad ; Kelley, Matthew W. ; Jiang, Li ; Tasman, William ; Zhang, Kang ; Nathans, Jeremy. / Vascular development in the retina and inner ear : Control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. In: Cell. 2004 ; Vol. 116, No. 6. pp. 883-895.
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