A mechanism of impaired mobility of oligodendrocyte progenitor cells by tenascin C through modification of wnt signaling

Abstract

In demyelinating diseases, the mechanisms of how oligodendrocyte (OLG) progenitor cells are affected in the demyelinated area remain to be elucidated. To investigate one aspect of the mechanisms, we focused on the role of tenascin C in regulating the migratory mobility of the progenitor cells via β‐catenin. By cDNA subtraction screening, we found tenascin C expression to be increased in OLG progenitors (rat primary O2A cells). Tenascin C inhibited the migration of OLG progenitors and CG‐4 cells, and β‐catenin accumulated at focal adhesions in these cells. These changes were associated with the inactivation of canonical wnt signaling. Overexpression of the wnt‐signaling antagonist Dapper prevented the migration of CG‐4 cells. This suggests that inactivation of the wnt signal is responsible for impaired migration of OLG caused by tenascin C. Our results suggest that tenascin C is involved in the impaired mobility of OLG progenitor cells through increased amounts of adhesion complex as well as the prevention of wnt signaling.