Myelin transcription factor 1 (Myt1) modulates the proliferation and differentiation of oligodendrocyte lineage cells
Myelin transcription factor 1 (Myt1) modulates the proliferation and differentiation of oligodendrocyte lineage cells
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DOI：
10.1016/j.mcn.2003.10.001
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发表时间：
2004-01-01
影响因子：
3.5
通讯作者：
Armstrong, RC
中科院分区：
文献类型：
--
作者：
Nielsen, JA;Berndt, JA;Armstrong, RC
髓磷脂转录因子1（Myt 1）是一种锌指DNA结合蛋白，在神经祖细胞和少突胶质细胞谱系细胞中表达。本研究通过过度表达假定的功能结构域，四锌指DNA结合区（4FMyt 1）或中央蛋白质-蛋白质相互作用结构域（CDMyt 1），而没有预测的转录激活结构域，来研究Myt 1在少突胶质细胞谱系细胞中的作用。在有丝分裂原的存在下，过表达4FMyt 1抑制少突胶质细胞祖细胞的增殖，但不抑制缺乏内源性Myt 1的细胞类型（星形胶质细胞和NIH 3 T3细胞）。通过形态学、免疫染色和髓磷脂基因表达评估，4FMyt 1的表达抑制少突胶质细胞祖细胞向少突胶质细胞的分化。祖细胞分化同样受到CDMyt 1表达的抑制，但仅部分受到完整Myt 1过表达的抑制。这些数据表明，Myt 1可能通过调节少突胶质细胞祖细胞增殖相对于终末分化和髓磷脂基因转录的上调来调节少突胶质细胞谱系发育中的关键转变点。爱思唯尔公司出版
Myelin transcription factor 1 (Myt1) is a zinc finger DNA-binding protein that is expressed in neural progenitors and oligodendrocyte lineage cells. This study examines the role of Myt1 in oligodendrocyte lineage cells by overexpressing putative functional domains, a four-zinc finger DNA-binding region (4FMyt1) or a central protein-protein interaction domain (CDMyt1), without the predicted transcriptional activation domain. In the presence of mitogens, overexpression of 4FMyt1 inhibited proliferation of oligodendrocyte progenitors, but not cell types (astrocytes and NIH3T3 cells) lacking endogenous Myt1. Expression of 4FMyt1 inhibited the differentiation of oligodendrocyte progenitors into oligodendrocytes as assessed by morphology, immunostaining, and myelin gene expression. Progenitor differentiation was similarly inhibited by expression of CDMyt1 but only partially suppressed by overexpression of the intact Myt1. These data indicate that Myt1 may regulate a critical transition point in oligodendrocyte lineage development by modulating oligodendrocyte progenitor proliferation relative to terminal differentiation and up-regulation of myelin gene transcription. Published by Elsevier Inc.