Regulation of the number of cell division rounds by tissue-specific transcription factors and Cdk inhibitor during ascidian embryogenesis.
Regulation of the number of cell division rounds by tissue-specific transcription factors and Cdk inhibitor during ascidian embryogenesis.
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在西顺式胚胎发生过程中，通过组织特异性转录因子和CDK抑制剂来调节细胞分裂的数量。
DOI：
10.1371/journal.pone.0090188
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nishida H
中科院分区：
文献类型：
--
作者：
Kuwajima M;Kumano G;Nishida H
在胚胎发生过程中，调节细胞分裂轮数的机制在很大程度上仍然是难以捉摸的。为了研究这个问题，我们使用了海鞘，它发育成具有少量细胞的蝌蚪幼虫。胚胎细胞从受精到孵化平均分裂11.45次。细胞分裂轮数根据胚胎谱系而变化。脊索和肌肉由大的有丝分裂后细胞组成，在发育中的胚胎早期停止分裂。在这里，我们表明，间充质转化为肌肉细胞命运的诱导FGF信号或肌肉特异性的关键转录因子Tbx 6的错误表达的抑制，改变了细胞分裂的数量，根据改变的命运。tbx 6可能激活一种假定的机制，在特定阶段停止细胞分裂。然而，Tbx 6的早熟表达对发育时钟本身的进展没有影响。细胞周期蛋白依赖性激酶抑制剂CKI-b的合子表达起始于肌肉，然后是脊索前体。CKI-b可能是脊索和肌肉组织特异性关键转录因子的下游。在两种不同的肌肉谱系中，有丝分裂后的肌肉细胞在9和8轮细胞分裂后产生，但最终的细胞分裂发生在相似的发育阶段。CKI-b基因表达在110细胞阶段同时在两种肌肉谱系中开始，这表明CKI-b蛋白积累在类似阶段停止细胞分裂。细胞分裂次数的差异可能是由于细胞周期长度的累积差异。这些结果表明，肌肉细胞不计数细胞分裂轮次的数量，并且在细胞命运确定后由组织特异性关键转录因子触发的CKI-b蛋白的积累可能作为一种计时器，测量细胞分裂终止前的时间。
Mechanisms that regulate the number of cell division rounds during embryogenesis have remained largely elusive. To investigate this issue, we used the ascidian, which develops into a tadpole larva with a small number of cells. The embryonic cells divide 11.45 times on average from fertilization to hatching. The number of cell division rounds varies depending on embryonic lineages. Notochord and muscle consist of large postmitotic cells and stop dividing early in developing embryos. Here we show that conversion of mesenchyme to muscle cell fates by inhibition of inductive FGF signaling or mis-expression of a muscle-specific key transcription factor for muscle differentiation, Tbx6, changed the number of cell divisions in accordance with the altered fate. Tbx6 likely activates a putative mechanism to halt cell division at a specific stage. However, precocious expression of Tbx6 has no effect on progression of the developmental clock itself. Zygotic expression of a cyclin-dependent kinase inhibitor, CKI-b, is initiated in muscle and then in notochord precursors. CKI-b is possibly downstream of tissue-specific key transcription factors of notochord and muscle. In the two distinct muscle lineages, postmitotic muscle cells are generated after 9 and 8 rounds of cell division depending on lineage, but the final cell divisions occur at a similar developmental stage. CKI-b gene expression starts simultaneously in both muscle lineages at the 110-cell stage, suggesting that CKI-b protein accumulation halts cell division at a similar stage. The difference in the number of cell divisions would be due to the cumulative difference in cell cycle length. These results suggest that muscle cells do not count the number of cell division rounds, and that accumulation of CKI-b protein triggered by tissue-specific key transcription factors after cell fate determination might act as a kind of timer that measures elapsed time before cell division termination.
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影响因子：
64.5
作者：
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通讯作者：
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