オリゴデンドロサイトの分化制御機構とオリゴデンドログリオーマの発生

Common Mechanism Underlying Oligodendrocyte Development and Oligodendrogliomagenesis

はじめに

　中枢神経系グリア細胞の1つオリゴデンドロサイトの発生はさまざまな細胞外因子および細胞内機構によって制御されている。例えば，sonic hedgehog（shh）はオリゴデンドロサイトの発生に重要な転写因子Olig1/Olig2とNkx2.2の発現を誘導し，オリゴデンドロサイト前駆細胞の発生を促す。逆にNotchおよび骨形成因子（bone morphogenic protein：BMP）は分化抑制因子Hes5とinhibitor-of-differentiation 4（Id4）の発現を誘導し，オリゴデンドロサイトの分化を抑制する。加えて血小板由来成長因子（platelet derived growth factor-AA：PDGF-AA），甲状腺ホルモン（thyroid hormone：TH），p53，p73，Wntなどの細胞内外因子もまたオリゴデンドロサイトの発生に重要な働きをしている。本稿ではオリゴデンドロサイト発生に関わる分子機構を概説し，オリゴデンドログリオーマ発生機構との関連および今後のオリゴデンドログリオーマ研究の方向性について論じる。

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.