Induction of oligodendrocyte differentiation by Olig2 and Sox10: Evidence for reciprocal interactions and dosage-dependent mechanisms
Induction of oligodendrocyte differentiation by Olig2 and Sox10: Evidence for reciprocal interactions and dosage-dependent mechanisms
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DOI：
10.1016/j.ydbio.2006.10.007
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发表时间：
2007-02-15
影响因子：
2.7
通讯作者：
Qiu, Mengsheng
中科院分区：
文献类型：
--
作者：
Liu, Zijing;Hu, Xuemei;Qiu, Mengsheng
最近的研究表明，少突胶质细胞的发育可能是在一个谱系特异性转录因子的层次结构的控制下。在发育中的小鼠脊髓中，Olig2、Sox10和Nkx2.2的表达在少突胶质细胞谱系的细胞中依次上调。这些转录因子在少突胶质细胞的特化和分化中起重要作用。然而，这些转录因子之间的调控关系和功能相互作用尚未确定。本研究系统地研究了Olig2、Sox10和Nkx2.2转录因子在少突胶质细胞分化调控中的功能和层次关系。结果发现，Olig2的过表达足以诱导胚胎鸡脊髓中Sox10、Nkx2.2和早熟少突胶质细胞分化。单独的Sox10表达也足以刺激异位少突胶质细胞分化并微弱地诱导Nkx2.2表达。尽管遗传证据表明Sox 10在Ofig 2下游发挥作用，但Sox 10活性可以调节Olig 2表达。此外，我们提出的证据表明，寡聚体2，Sox 10和Nkx 2.2的少突胶质细胞分化的控制是一个剂量依赖性的发育过程，可以受到单倍不足和过量。(c)2006年爱思唯尔公司All rights reserved.
Recent studies have suggested that oligodendrocyte development is likely to be under the control of a hierarchy of lineage-specific transcription factors. In the developing mouse spinal cord, expression of Olig2, Sox10 and Nkx2.2 is sequentially up-regulated in cells of oligodendrocyte lineage. These transcription factors play essential roles in oligodendrocyte specification and differentiation. However, the regulatory relationship and functional interactions among these transcription factors have not been determined. In this study, we systematically investigated the function and hierarchical relationship of Olig2, Sox10 and Nkx2.2 transcription factors in the control of oligodendrocyte differentiation. It was found that over-expression of Olig2 is sufficient to induce Sox10, Nkx2.2 and precocious oligodendrocyte differentiation in embryonic chicken spinal cord. Sox10 expression alone is also sufficient to stimulate ectopic oligodendrocyte differentiation and weakly induce Nkx2.2 expression. Although genetic evidence indicated that Sox10 functions downstream of Ofig2, Sox10 activity can modulate Olig2 expression. In addition, we presented evidence that the control of oligodendrocyte differentiation by Olig2, Sox10 and Nkx2.2 is a dosagedependent developmental process and can be affected by both haploinsufficiency and over-dosage. (c) 2006 Elsevier Inc. All rights reserved.