Journal Article

Cdon acts as a Hedgehog decoy receptor during proximal-distal patterning of the optic vesicle

Gestri, Gaia, Sánchez-Arrones, Luisa, Wilson, Stephen W., Cardozo, Marcos Julián, Sánchez-Camacho, Cristina, Bovolenta, Paola, Guerrero, Isabel, Sandonis, África

2014

Overview

Patterning of the vertebrate optic vesicle into proximal/optic stalk and distal/neural retina involves midline-derived Hedgehog (Hh) signalling, which promotes stalk specification. In the absence of Hh signalling, the stalks are not specified, causing cyclopia. Recent studies showed that the cell adhesion molecule Cdon forms a heteromeric complex with the Hh receptor Patched 1 (Ptc1). This receptor complex binds Hh and enhances signalling activation, indicating that Cdon positively regulates the pathway. Here we show that in the developing zebrafish and chick optic vesicle, in which cdon and ptc1 are expressed with a complementary pattern, Cdon acts as a negative Hh signalling regulator. Cdon predominantly localizes to the basolateral side of neuroepithelial cells, promotes the enlargement of the neuroepithelial basal end-foot and traps Hh protein, thereby limiting its dispersion. This Ptc-independent function protects the retinal primordium from Hh activity, defines the stalk/retina boundary and thus the correct proximo-distal patterning of the eye. The Drosophila homologue of the vertebrate cell surface glycoprotein Cdon binds Hedgehog ligand and thereby prevents its diffusion. Here, the authors provide evidence for a similar mechanism during vertebrate optic vesicle patterning, where Cdon acts as a negative regulator of Hedgehog signalling to define the boundary between the optic stalk and the retina.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
• Subject: 14/34 / 14/63 / 42/44 / 631/136/756 / 631/80/86 / 64/116 / 96/1 / 96/109 / 96/44 / Animals / Animals, Genetically Modified / Binding Sites / Body Patterning / Cell Adhesion Molecules - metabolism / Chick Embryo / Eye - embryology / Hedgehog Proteins - metabolism / HEK293 Cells / Humanities and Social Sciences / Humans / Membrane Proteins / multidisciplinary / Neural Cell Adhesion Molecules - metabolism / Patched Receptors / Patched-1 Receptor / Receptors, Cell Surface - metabolism / Science / Science (multidisciplinary) / Zebrafish / Zebrafish Proteins - metabolism