Coordination between cell identity, tissue mechanics and proportionate patterning during vertebrate eye formation
The development of an organ requires the precise coordination between pattern formation, morphogenetic movements and the final size of the system. Significant progress has been made in understanding these processes independently. The aim of this proposal is to integrate this information by analyzing coordination hubs, such as the crosstalk between YAP/TAZ and Wntβ-catenin pathways during the specification of the identity and the mechanical properties of the cell. I will use the development of the vertebrate eye as a defined paradigm. To identify intrinsic and relevant properties of this system, the two most powerful and amenable models of eye morphogenesis will be analyzed: the self-generation of 3D optic cups from mouse Embryonic Stem Cells and the in vivo development of the teleost eye. The plan is to generate a spatiotemporal activation map of the main determinants of eye identity and use them to link morphogen signaling with key morphogenetic processes in specific cells. This will be the groundwork to identify the role of retinal pigmented epithelial (RPE) cells during optic cup folding, the context that I will use to understand both the coordination between morphogen patterning (Wnt) and mechanical properties (Yap) of the retinal precursors, and between proportionated patterning and eye size (scale-invariant mechanisms). This proposal relies on the collaboration of multiple experts from the host institute and on the use of already developed bona fide protocols, reporter lines and signaling perturbations experiments, but revisited with cutting-edge technologies, such as light sheet microscopy and computational modeling. Thus, it is an extremely innovative but feasible project to understand deep-root questions of organ formation. Moreover, this interdisciplinary project will open unprecedented opportunities in the field of organ regeneration from a comprehensive morphogenetic perspective, which will be the foundation of my future independent research.