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

Marcos Julián Cardozo, Luisa Sánchez-Arrones, África Sandonis, Cristina Sánchez-Camacho, Gaia Gestri, Stephen W. Wilson, Isabel Guerrero and Paola Bovolenta ()
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Marcos Julián Cardozo: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas—Universidad Autónoma de Madrid
Luisa Sánchez-Arrones: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas—Universidad Autónoma de Madrid
África Sandonis: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas—Universidad Autónoma de Madrid
Cristina Sánchez-Camacho: Ciber de Enfermedades Raras (CIBERER), ISCIII
Gaia Gestri: University College London
Stephen W. Wilson: University College London
Isabel Guerrero: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas—Universidad Autónoma de Madrid
Paola Bovolenta: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas—Universidad Autónoma de Madrid

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms5272

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