Final Report Summary - ZEYMORPH (Celluar and Molecular Bases of Vertebrate Eye Morphogenesis)
Understanding morphogenesis, or how our organs and tissues are shaped during embryogenesis, is fundamental to understand how our body forms and thus functions. Indeed morphogenetic defects often alter the correct function of our organs. Despite its evident relevance, our knowledge of morphogenesis is limited, probably because it is a complex process in which changes in cell shape, adhesion properties and migration patterns happen simultaneously, hindering a fine analysis. In this project we have taken advantage of the advanced imaging and genetic tools available in the zebrafish to analyse the early stages of eye morphogenesis, a very poorly understood process that, when perturbed, results in congenital eye malformations.
The data generated allowed to characterise some of the relevant molecular mechanisms and to propose a model of the cell and tissue rearrangements underlying early stages of eye morphogenesis. The acquisition of eye identity by a group of cells in the primordium of the brain is followed by their segregation from the surrounding cells, in a process that we have shown to require the activation of a group of molecules known as Ephrins. We have also shown that during optic vesicle evagination eye cells polarise, elongate and intercalate radially among each other, in a process that we propose promotes the lateral expansion of the optic primordia. Some of our most recent work provides compelling evidence of a role for the signalling molecule Wnt11 in controlling these eye cell behaviours.
As the optic vesicles evaginate, they become partitioned in smaller subdomains, with different cellular identities. These two processes (morphogenesis and patterning) have to be tightly coordinated to give rise to a functional organ. Our studies addressed this issue, showing that the first patterning event occurs at the onset of optic vesicle evagination and requires the coordinated function of the Hedgehog (Hh) and Fibroblast-growth-factor (Fgf) signalling factors. We are currently extending these studies to determine how the establishment of regional fates in the optic primordia by Hh and Fgfs is coordinated with the dynamic cell rearrangements observed during their evagination, by monitoring eye fate acquisition in vivo.
Our findings not only constitute a conceptual advance in our understanding of eye morphogenesis but have also generated new tools that will be freely available for other researchers in the fish community.
During the course of the project, the fellow well-integrated in the research environment of her institution and participated in the organisation of seminar series and outreach activities. Her expertise in zebrafish development and morphogenesis has contributed to consolidate the fish as an alternative model system at her institution. Several students have been trained under the fellow’s supervision, and she is currently co-supervising two PhD students whose projects are related to the topic of this Grant. In addition to the funding awarded by the Marie Curie CIG Program, the fellow has obtained funding from other sources, which has allowed her to continue with her line of research and to promote her independency.
The data generated allowed to characterise some of the relevant molecular mechanisms and to propose a model of the cell and tissue rearrangements underlying early stages of eye morphogenesis. The acquisition of eye identity by a group of cells in the primordium of the brain is followed by their segregation from the surrounding cells, in a process that we have shown to require the activation of a group of molecules known as Ephrins. We have also shown that during optic vesicle evagination eye cells polarise, elongate and intercalate radially among each other, in a process that we propose promotes the lateral expansion of the optic primordia. Some of our most recent work provides compelling evidence of a role for the signalling molecule Wnt11 in controlling these eye cell behaviours.
As the optic vesicles evaginate, they become partitioned in smaller subdomains, with different cellular identities. These two processes (morphogenesis and patterning) have to be tightly coordinated to give rise to a functional organ. Our studies addressed this issue, showing that the first patterning event occurs at the onset of optic vesicle evagination and requires the coordinated function of the Hedgehog (Hh) and Fibroblast-growth-factor (Fgf) signalling factors. We are currently extending these studies to determine how the establishment of regional fates in the optic primordia by Hh and Fgfs is coordinated with the dynamic cell rearrangements observed during their evagination, by monitoring eye fate acquisition in vivo.
Our findings not only constitute a conceptual advance in our understanding of eye morphogenesis but have also generated new tools that will be freely available for other researchers in the fish community.
During the course of the project, the fellow well-integrated in the research environment of her institution and participated in the organisation of seminar series and outreach activities. Her expertise in zebrafish development and morphogenesis has contributed to consolidate the fish as an alternative model system at her institution. Several students have been trained under the fellow’s supervision, and she is currently co-supervising two PhD students whose projects are related to the topic of this Grant. In addition to the funding awarded by the Marie Curie CIG Program, the fellow has obtained funding from other sources, which has allowed her to continue with her line of research and to promote her independency.