Gene regulation and morphogenesis

How is the formation of an organ so amazingly robust and reproducible? This perfection is achieved by the tightly coordinated teamwork between diverse components, which are instructing very different cellular processes with a common goal: to form a functional proportionated organ. One of the challenges of our research group is to identify coordination hubs between the signaling inputs that will ultimately control organ 3D shape.
The first hub we want to identify is the one between biochemical signaling and tissue mechanics. Specifically, the biochemical signaling that results in cell identity specification (Wnt signaling) and the morphogenetic information that depends on the mechanical properties of cells and tissues (mediated by YAP signaling).
The second hub we want to understand is between patterning and organ size. This mechanism will guarantee that the different fractions of the organ are present in a proportional manner with respect to the final size of the organ, and of the organism. We will evaluate scale-invariant models to identify the molecular mechanisms that not only pattern the eye, but also do so in a proportionated way.
To answer these questions we use the development of the zebrafish eye as a paradigm of organ formation.

 

 

 

Finally, once we have a comprehensive view on the integration of cell fate signaling, mechanics and tissue scaling during the formation of the vertebrate eye, we want to analyze if the organismal context is indispensable for it. For that, I plan to study eye organoids grown up outside the organism, such as in vitro 3D generated optic cups from mouse Embryonic Stem Cells (mESCs). Under permissive conditions, mESCs cultures spontaneously generate three-dimensional (3D) optic cups without any external input. This finding is very powerful in terms of applications in retinal regenerative medicine, but caution should be taken since the in vivo scenario is much more complex, where signals and forces from external structures as well as the spatial constrains of the organism, would be most probably improving the robustness and plasticity of organ formation. To dig deeper into this amazing question, I will compare properties of the in vivo development of the eye in zebrafish with the in vitro 3D generation of the optic cups. These systems are very amenable and ideal for in-toto 4D imaging, for tracking cell movements and cell shape rearrangements, as well as for applying different perturbations, such as mutagenesis, drug treatments or mechanical interferences of the tissue.