The vertebrate retina is an important outpost of the central nervous system, responsible for the perception and transmission of visual information. It consists of five different types of neurons that reproducibly laminate into three layers, a process of crucial importance for the organ’s function. Unsurprisingly, impaired fate decisions as well as impaired neuronal migrations and lamination lead to impaired retinal function. However, how processes are coordinated at the cellular and tissue level and how variable or robust retinal formation is, is currently still underexplored. In my lab, we aim to shed light on these questions from different angles, studying on the one hand differentiation phenomena and their variability and on the other hand the downstream migration and lamination phenomena. We use zebrafish as our main model system due to its excellent possibilities for live imaging and quantitative developmental biology. More recently we also started to use human retinal organoids as a comparative system. We further employ cross disciplinary approaches to address these issues combining work of cell and developmental biology, biomechanics, theory and computer science. Together, this allows us to integrate cell with tissue-wide phenomena and generate an appreciation of the reproducibility and variability of events.

Embryo morphogenesis is impacted by dynamic changes in tissue material properties, which have been proposed to occur via processes akin phase transitions (PTs). Here, we show that rigidity percolation provides a simple and robust theoretical framework to predict material/structural PTs of embryonic tissues from local cell connectivity. By using percolation theory, combined with directly monitoring dynamic changes in tissue rheology and cell contact mechanics, we demonstrate that the zebrafish blastoderm undergoes a genuine rigidity PT, brought about by a small reduction in adhesion-dependent cell connectivity below a critical value. We quantitatively predict and experimentally verify hallmarks of PTs, including power-law exponents and associated discontinuities of macroscopic observables at criticality. Finally, we show that this uniform PT depends on blastoderm cells undergoing meta-synchronous divisions causing random and, consequently, uniform changes in cell connectivity. Collectively, our theoretical and experimental findings reveal the structural basis of material PTs in an organismal context.