Stochastic Single Cell Behaviour Leads to Robust Horizontal Cell Layer Formation in the Vertebrate Retina

Abstract

ABSTRACTDevelopmental programs that arrange cells and tissues into patterned organs are remarkably robust. In the developing vertebrate retina for example, neurons reproducibly assemble into distinct layers giving the mature organ its overall structured appearance. This stereotypic neuronal arrangement, termed lamination, is important for efficient neuronal connectivity. While retinal lamination is conserved in many vertebrates including humans, how it emerges from single cell behaviour is not fully understood. To shed light on this question, we here investigated the formation of the retinal horizontal cell layer. Using in vivo light sheet imaging of the developing zebrafish retina, we generated a comprehensive quantitative analysis of horizontal single cell behaviour from birth to final positioning. Interestingly, we find that all parameters analyzed including cell cycle dynamics, migration paths and kinetics as well as sister cell dispersal are very heterogeneous. Thus, horizontal cells show individual non-stereotypic behaviour before final positioning. Yet, these initially stochastic cell dynamics always generate the correct laminar pattern. Consequently, our data shows that lamination of the vertebrate retina contains a yet underexplored extent of single cell stochasticity.