Elucidating Novel Roles of Oligodendrocyte Precursor Cells that Shape Nervous System Structure and Function

Oligodendrocyte precursor cells (OPCs) have an established role in generating myelinating oligodendrocytes. However, many undifferentiated OPCs reside throughout the CNS lifelong suggesting additional, yet unclear roles of this cell population in regulating CNS form and function. Recently, my group has revealed that OPCs can sculpt neuronal connections, indicating that this cell type indeed has fundamental roles besides myelin generation. However, we do not know how OPCs exert these functions, nor do we know how resident OPCs integrate into neuronal networks, how they communicate with surrounding neurons, and how this communication shapes neural circuit assembly. Here, I propose a multiscale approach using zebrafish as model organism in which we use gene expression analysis, gene targetting and manipulation of neuronal activity, combined with structural in vivo imaging, physiological and behavioural analyses. Using these assays, we will determine how individual OPCs are integrated in a defined neural network and how they contribute to activity-dependent refinement of neuronal connectivity. Furthermore, we will elucidate the genetic code by which individual OPCs mediate connectivity between neurons and test how dysfunctional OPCs affect circuit assembly and animal behaviour. Together, this will reveal novel roles of OPCs for circuit formation, function and dysfunction.