ARP2/3 complex is required for directional migration of neural stem cell-derived oligodendrocyte precursors in electric fields

Click on the DOI link to access the article (may not be free).Introduction: The loss of oligodendrocytes in a lesion of the central nervous system causes demyelination and therefore impairs axon function and survival. Transplantation of neural stem cell-derived oligodendrocyte precursor cells (NSC-OPCs) results in increased oligodendrocyte formation and enhanced remyelination. The directional migration of grafted cells to the target can promote the establishment of functional reconnection and myelination in the process of neural regeneration. Endogenous electric fields (EFs) that were detected in the development of the central nervous system can regulate cell migration. Methods: NSCs were isolated from the brains of ARPC2(+/+) and ARPC2(-/-) mouse embryo and differentiated into OPCs. After differentiation, the cultured oligospheres were stimulated with EFs (50, 100, or 200 mV/mm). The migration of OPCs from oligospheres was recorded using time-lapse microscopy. The cell migration directedness and speed were analyzed and quantified. Results: In this study, we found that NSC-OPCs migrated toward the cathode pole in EFs. The directedness and displacement of cathodal migration increased significantly when the EF strength increased from 50 to 200 mV/mm. However, the EF did not significantly change the cell migration speed. We also showed that the migration speed of ARPC2(-/-) OPCs, deficient in the actin-related proteins 2 and 3 (ARP2/3) complex, was significantly lower than that of wild type of OPCs. ARPC2(-/-) OPCs migrated randomly in EFs. Conclusions: The migration direction of NSC-OPCs can be controlled by EFs. The function of the ARP complex is required for the cathodal migration of NSC-OPCs in EFs. EF-guided cell migration is an effective model to understanding the intracellular signaling pathway in the regulation of cell migration directness and motility.This work was supported by LY's start-up funding, Wichita State University, and an Institutional Development Award from the National Institute of General Medical Sciences of the National Institutes of Health under grants P20 GM103418 (to LY) and NIH PO1 GM066311 (to RL)