Geometric principles determining the morphology of oligodendrocyte precursor cells in brain white matter

Abstract

We used transgenic mice expressing membrane-tagged green fluorescence protein in the oligodendrocyte precursor cells (OPCs), high-resolution imaging, and detailed quantitative morphometric analysis to investigate the geometrical principles that govern structural organization of OPCs in the mouse corpus callosum. Our major findings are: (1) During the first two months of postnatal life in mice, total length of all OPCs processes increases via elaboration of new branches from the existing processes rather than via the appearance of new processes; (2) New branches are preferentially added to more distal sites of OPCs processes; (3) The processes of OPCs show stronger preferential alignment with the posterior-anterior brain axis rather than with the lateral-medial or dorsal-ventral brain axes; at the same time, the processes of OPCs show stronger preferential alignment with the lateral-medial than with the dorsal-ventral brain axis. Our study is the first detailed comprehensive analysis of OPCs morphology comparable to those available for neurons. It helps understanding the geometrical principles that govern structural organization of OPCs. These principles are important when taking into account that OPCs receive synaptic input from neurons and are capable of synaptic integration. Arborization and structural organization of OPCs processes is expected to influence the travel of synaptic input from the processes (where synapses are located) to the cell soma (where synaptic inputs are integrated), in analogy to how it occurs in neurons. Hence, the integrated synaptic signal at the OPCs cell soma which is likely to influence development and behavior of OPCs will depend on the cell morphology. Main PointsO_LIOPC maturation increases process length through higher-order branching. C_LIO_LINew branches are added distally while preserving local architecture of the inner domain. C_LIO_LIThe processes change their orientation depending on the local micro-environment. C_LI