In most brain regions, developing neurons are arranged into distinct layers giving the mature tissue its stratified appearance. For successful lamination, neurons must move to the correct place after their birth. Defective neuronal migration and lamination can cause pathological brain conditions, including cognitive defects and drug-resistant epilepsy.
While neuronal migration and lamination is well explored in the mammalian neocortex, particularly in rodents, it is less well understood in other parts of the central nervous system. Furthermore, many previous studies have concentrated on cellular mechanisms that drive cortical different neuronal migration modes. While these cellular mechanisms are often understood to the molecular detail, how cell-tissue interplay and particularly the physical environment of migrating cells influence the process is less known.
This is particularly true for the vertebrate retina, an important outpost of the central nervous system responsible for the perception of the visual environment. Here five types of neurons reproducibly laminate into three layers, a process of crucial importance for the organ’s function. Thus, unsurprisingly, neuronal layering defects lead to impaired retinal function. However, how lamination is achieved at the cellular and tissue level and how it is orchestrated in a tissue in which different neurons move concomitantly in different directions is little understood.
This work plan is an important step in understanding this intricate process. Not only do we explore how single cells migrate and orient themselves in a crowded tissue but we also take cell-cell and cell-tissue interplay into account. To this end, we carry out cross-disciplinary studies that involve cell and developmental biologists, experts in biomechanics, theorists and computer scientists. This holistic approach allows us to go beyond the state of the art and integrate and interpret cell and tissue wide phenomena. Our findings are backed up by theoretical models that generate a deeper appreciation of the different phenomena studies. The fact that findings are compared between species, zebrafish and humans as well as human organoids provides the unique opportunity to dissect the nature of species-specific differences in comparison to the in vivo versus an ex vivo environment.
While this project focuses on neural lamination in the retina, findings will also inspire future cross-disciplinary studies that investigate neuronal lamination in other parts of the brain.
