How to Build an Eye - Dissecting the coordination between cellular rearrangements and the interplay with material properties of the tissue during Optic Cup Morphogenesis

Project Information

HowToBE

Grant agreement ID: 101038054

DOI

10.3030/101038054

Project closed

EC signature date 31 March 2021

Start date 1 March 2022

End date 29 February 2024

Funded under

• SPREADING EXCELLENCE AND WIDENING PARTICIPATION

Total cost

€ 147 815,04

EU contribution

€ 147 815,04

Coordinated by

FUNDACAO CALOUSTE GULBENKIAN
Portugal

Periodic Reporting for period 1 - HowToBE (How to Build an Eye - Dissecting the coordination between cellular rearrangements and the interplay with material properties of the tissue during Optic Cup Morphogenesis)

Reporting period: 2022-03-01 to 2024-02-29

Summary of the context and overall objectives of the project

Building an organ is a multistep process in which correct morphogenesis emerges from feedback loops involving tight genetic control and mechanical forces. During organogenesis, discrete morphogenetic events (such as cell migration, intercalation or epithelia invagination) lead to the formation of 3-dimensional organs. One very prominent morphogenetic phenomenon driving organogenesis is the emergence of curvature in epithelia, which lays the architectural foundations for critical developmental processes. So far, the biomechanical interactions that lead to shape emergence have been mainly studied in ex vivo systems or in vivo for two-dimensional shape changes. Thus, we still lack comprehensive quantitative studies in vivo and in 3D, which would bring a multidimensional perspective to understanding organ formation.
To address this problem, we studied the morphogenesis of a complex curved 3D tissue, the vertebrate optic cup (OC), the precursor of the retina, where the different cell and tissue rearrangements can be studied in native 4D conditions.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In zebrafish, during invagination of the OC, three epithelial rearrangements take place in distinct areas: Rim cell migration, epithelial flattening, and basal foot shrinkage. Given the concurrent dynamics of these processes, we hypothesized that a combinatorial mechanical strategy is needed to achieve the final OC shape in a robust manner. We disrupted single rearrangements to study the interplay between the different cellular rearrangements and how they influence each other mechanically. We then analyzed how such disruptions influenced the other processes and if they interfered with the overall OC shape. To perform such analysis we used 4D segmentation of the different epithelia and of the single cells that compose them. We found that, even though the epithelial rearrangements occur concurrently (rim cell migration, epithelial flattening, and basal foot shrinkage), they do not influence each other and occur independently. Furthermore, the OC invagination can proceed upon disruption of one of those events, suggesting a strong robustness of this morphogenetic process. Analysis and description of shape changes, at cell and tissue level, during OC morphogenesis, together with the theoretical model of tissue invagination, allowed us to understand how the tissue is curving and which are the major players during this process.


This work, both theoretically and experimentally, contributes to the overall understanding of the formation of complex curved organs. The respective manuscript is being prepared and will be published in open-access format. The data will be available in public repositories when possible or upon request by other researchers.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This project adds to the current state of the art by studying, in 4 dimensions (3D + time), the detailed shape changes and the complex interactions that occur during the morphogenesis of a curved tissue in vivo. Such detailed description with an in vivo context is at the forefront of the study of tissue morphogenesis.
Until the end of the project, we expect to uncover the main driver of Optic Cup invagination and finish the theoretical model. The results will be published by the end of the year in an article with open acess format .

3D reconstruction of fully formed Optic Cup, seen in different orientations