TAPP1 inhibits the differentiation of oligodendrocyte precursor cells via suppressing the Mek/Erk pathway.

Abstract

Oligodendrocytes (OLs) are glial cells that form myelin sheaths around axons in the central nervous system (CNS). Loss of the myelin sheath in demyelinating and neurodegenerative diseases can lead to severe impairment of movement. Understanding the extracellular signals and intracellular factors that regulate OL differentiation and myelination during development can help to develop novel strategies for enhancing myelin repair in neurological disorders. Here, we report that TAPP1 was selectively expressed in differentiating OL precursor cells (OPCs). TAPP1 knockdown promoted OL differentiation and myelin gene expression in culture. Conversely, over-expression of TAPP1 in immature OPCs suppressed their differentiation. Moreover, TAPP1 inhibition in OPCs altered the expression of Erk1/2 but not AKT. Taken together, our results identify TAPP1 as an important negative regulator of OPC differentiation through the Mek/Erk signaling pathway.