MechaPattern · Coordination between cell identity, tissue mechanics and proportionate patterning during vertebrate eye formation

Coordination between cell identity, tissue mechanics and proportionate patterning during vertebrate eye formation

The generation of organs depends on the integration of different sources of information. The most relevant ones are cell identity information given by signaling genetic pathways and the inherent mechanical information of individual cells and tissues. In addition, these different inputs must be coordinated in a way that the organ is scaled and patterned proportionally to their final size. Although some of these aspects have been extensively studied independently, a comprehensive analysis about how they are integrated is missing. The first aim of this proposal is to understand the coordination between these interdependent sources of morphogenetic cues using as a paradigm the development of the vertebrate eye. Eye formation is described as a two-step process; first, the evagination of the eye progenitors to form the optic vesicles, and second, the infolding of the tissue into bi-layered optic cups. Two main territories are specified within the vertebrate optic cup: the inner layer, called neuroretina (NR) and the surrounding outer layer, the retinal pigmented epithelium (RPE). Decades of research have demonstrated that the development of a functional eye requires the interplay of different genetic programs, which are mostly driven by signaling pathways, together with physical forces and extracellular matrix mechanics. One of the biggest challenges in the field is to find coordination hubs between signaling genes that control cell fate decisions and mechanical properties of the tissue that drive cell collectives movements and ultimately control organ 3D shape. YAP, the Hippo nuclear transducer, is the perfect candidate to mediate this coordination, since it is able to sense and infer tissue mechanical inputs and it interacts with multiple signaling pathways. These mechano-patterning interplay and scaling-invariant properties are needed to grant plasticity and adaptability to organs and tissues, essential attributes for processes such as homeostasis or regeneration. Therefore, this understanding about organ formation from a comprehensive morphogenetic and proportionate patterning perspective is required to establish the biological groundwork for next generation regenerative medicine. To contribute to this innovative field, I plan to compare properties of in vivo models of eye formation with in vitro 3D eye organoids generated from mouse Embryonic Stem Cells (mESCs). The second aim of the proposal is to analyze the maintenance of this morphogenetic and mechanical coordination in these organoids grown up outside the organism.

Data: CORDIS, © European Union