CHI-ZEF · Cdon-Hh Interaction: functional in vivo analysis in zebrafish

Cdon-Hh Interaction: functional in vivo analysis in zebrafish

Patterning of the vertebrate optic vesicle into proximal/optic stalk and distal/neural retina involves midline-derived Hh signalling, which promotes stalk specification. In the absence of Hh signalling, the stalk is not specified, forming a single cyclopic eye. Work from the hosting laboratory has shown that the cell adhesion molecule Cdon presents a complementary expression pattern to the canonical Hh receptor Ptc and acts as a negative Hh signalling regulator during the formation of the eye in zebrafish. At the neural retina/optic stalk border Cdon binds Hh, serving as a decoy receptor to protect the neural retina from Hh activity, likely preventing its diffusion and limiting its long-range signalling. How Cdon controls Hh dispersion shaping the gradient responsible for the correct P-D patterning of the eye remains unknown. Furthermore and although cell-to-cell communication mediated by morphogen signalling has been widely studied, there is surprisingly little information about the mechanistic insights of its spatial-temporal occurrence. This project attempted to explore these mechanisms during early stages of eye development, with the aim of providing a better understanding of Hh dispersion in the nervous system. In particular, we sought to focus on the impact that membrane bound molecules have in shaping Hh gradients and its consequence on tissue morphogenesis. Using zebrafish, CRISPR/Cas9 technology and advanced imaging we attempted generate cutting-edge tools to follow in vivo Hh/Cdon interaction during zebrafish eye formation. We envisioned that a better knowledge of tissue morphogenesis would immediately revert into the field of regenerative medicine, which attempts to recreate tissue and organs in non-developmental contexts, a goal that requires a deep understanding of developmental principles. The successful development of the project should have also provided key technical developments and useful information for clinical research towards prevention and treatment of congenital ocular malformations. Although not lethal, eye pathologies are severely impairing diseases with an important socio-economical charge for the society. Their prevention and treatment would thus represent an important step forward in the life of many people.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз