Cdon-Hh Interaction: functional in vivo analysis in zebrafish

ended

Patterning of the vertebrate optic vesicle into proximal/optic stalk and distal/neural retina involves midline-derived Hh signalling, which promotes stalk specification. At the neural retina/optic stalk border, the cell adhesion molecule Cdon binds Hh, acting as a decoy receptor to protect the neural retina from Hh activity. How Cdon controls Hh dispersion, what is the destiny of the Hh protein accumulated at the neural retina/optic stalk boundary, whether Cdon participates in the release of Hh from its producing cells or whether Cdon has Hh-unrelated functions in the neural retina are the arising and still unanswered questions I aim to tackle in this proposal. Using the zebrafish as a model system and CRISPR/Cas9 technology I will first generate unprecedented tools to follow in vivo Cdon/Hh interaction, and then address how Cdon, expressed in both the ventral diencephalic midline and the neural retina, shapes the gradient of Hh responsible for proximo-distal patterning of the eye. I expect that the development of this proposal will provide significant advance on how morphogenetic signalling pathways operate, ultimately reverting into the field of regenerative medicine and clinical research related to congenital ocular malformations.