Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells

Abstract

Cell migration is critical for brain development and linked to several neurodevelopmental disorders, including schizophrenia. We have shown previously that cell migration is dysregulated in olfactory neural stem cells from people with schizophrenia. Although they moved faster than control cells on plastic substrates, patient cells were insensitive to regulation by extracellular matrix proteins, which increase the speeds of control cells. As well as speed, cell migration is also described by directional persistence, the straightness of movement. The aim of this study was to determine whether directional persistence is dysregulated in schizophrenia patient cells and whether it is modified on extracellular matrix proteins. Directional persistence in patient-derived and control-derived olfactory cells was quantified from automated live-cell imaging of migrating cells. On plastic substrates, patient cells were more persistent than control cells, with straighter trajectories and smaller turn angles. On most extracellular matrix proteins, persistence increased in patient and control cells in a concentration-dependent manner, but patient cells remained more persistent. Patient cells therefore have a subtle but complex phenotype in migration speed and persistence on most extracellular matrix protein substrates compared to control cells. If present in the developing brain, this could lead to altered brain development in schizophrenia.