[Common mechanism underlying oligodendrocyte development and oligodendrogliomagenesis]

Abstract

A number of extrinsic factors and intracellular mechanisms have been revealed to be involved in oligodendrocyte development. For instance, sonic hedgehog induces the expression of basic helix-loop-helix (bHLH) transcription factors, Olig1 and Olig2, and a homeobox transcription factor Nkx2.2, both of which induce neural stem cells (NSCs) to differentiate into oligodendrocyte precursor cells when the factors work together. In contrast, Notch and bone morphogenic proteins (BMP) block oligodendrocyte differentiation by inducing the expression of the transcription inhibitors Hes5 and Id4, respectively. Moreover, it was shown that other extrinsic and intrinsic factors, including platelet derived growth factor, thyroid hormone (TH), TH receptors, p53, and Wnt, are also involved in the development, positively or negatively. It has been thought that oligodendroglioma, one of brain tumors, is generated from oligodendrocyte lineage cells as the tumor cells share characteristics of oligodendrocyte, such as the honeycomb structure, and the expression of oligodendrocyte-related factors, including Olig2 and NG2 proteoglycan. However, recent progress in the field revealed that oligodendroglioma might be generated from NSCs and astrocytes as well as oligodendrocyte lineage cells. Therefore, it is crucial to investigate the cell-of-origin of oligodendroglioma and to identify target genes and markers for the therapy. In this review, I summarize the mechanism of oligodendrocyte development and present how the oligodendrocyte research can help to understand and to investigate the mechanism of oligodendroglioma development.