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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT
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Putative oncogene Brachyury (T) is essential to specify cell fate but dispensable for notochord progenitor proliferation and EMT

机译：推定的癌基因Brachyury（T）对于确定细胞命运至关重要但对于脊索祖细胞增殖和EMT而言是必不可少的

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摘要

The transcription factor Brachyury (T) gene is expressed throughout primary mesoderm (primitive streak and notochord) during early embryonic development and has been strongly implicated in the genesis of chordoma, a sarcoma of notochord cell origin. Additionally, T expression has been found in and proposed to play a role in promoting epithelial–mesenchymal transition (EMT) in various other types of human tumors. However, the role of T in normal mammalian notochord development and function is still not well-understood. We have generated an inducible knockdown model to efficiently and selectively deplete T from notochord in mouse embryos. In combination with genetic lineage tracing, we show that T function is essential for maintaining notochord cell fate and function. Progenitors adopt predominantly a neural fate in the absence of T, consistent with an origin from a common chordoneural progenitor. However, T function is dispensable for progenitor cell survival, proliferation, and EMT, which has implications for the therapeutic targeting of T in chordoma and other cancers.
机译：转录因子Brachyury（T）基因在早期胚胎发育过程中在整个中胚层（原始条带和脊索）中表达，并与脊索瘤（脊索细胞起源的肉瘤）的发生密切相关。此外，已经发现T表达在各种其他类型的人类肿瘤中促进上皮-间质转化（EMT）并发挥作用。但是，T在正常哺乳动物脊索的发育和功能中的作用仍未被很好地理解。我们已经生成了一种诱导型敲低模型，以有效和选择性地从小鼠胚胎中的脊索中消耗T。结合遗传谱系追踪，我们表明T功能对于维持脊索细胞的命运和功能至关重要。祖细胞在不存在T的情况下主要采用神经命运，这与普通软骨神经祖细胞的起源一致。但是，T功能对于祖细胞的存活，增殖和EMT是必不可少的，这对脊索瘤和其他癌症中T的治疗靶向具有影响。

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