• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Development >Sub-circuits of a gene regulatory network control a developmental epithelial-mesenchymal transition
【24h】

Sub-circuits of a gene regulatory network control a developmental epithelial-mesenchymal transition

机译：基因调控网络的子电路控制发育上皮-间质转化

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Epithelial-mesenchymal transition (EMT) is a fundamental cell state change that transforms epithelial to mesenchymal cells during embryonic development, adult tissue repair and cancer metastasis. EMT includes a complex series of intermediate cell state changes including remodeling of the basement membrane, apical constriction, epithelial de-adhesion, directed motility, loss of apical-basal polarity, and acquisition of mesenchymal adhesion and polarity. Transcriptional regulatory state changes must ultimately coordinate the timing and execution of these cell biological processes. A wellcharacterized gene regulatory network (GRN) in the sea urchin embryo was used to identify the transcription factors that control five distinct cell changes during EMT. Single transcription factors were perturbed and the consequences followed with in vivo time-lapse imaging or immunostaining assays. The data show that five different sub-circuits of the GRN control five distinct cell biological activities, each part of the complex EMT process. Thirteen transcription factors (TFs) expressed specifically in pre-EMT cells were required for EMT. Three TFs highest in the GRN specified and activated EMT (alx1, ets1, tbr) and the 10 TFs downstream of those (tel, erg, hex, tgif, snail, twist, foxn2/3, dri, foxb, foxo) were also required for EMT. No single TF functioned in all five sub-circuits, indicating that there is no EMT master regulator. Instead, the resulting sub-circuit topologies suggest EMT requires multiple simultaneous regulatory mechanisms: forward cascades, parallel inputs and positive-feedback lock downs. The interconnected and overlapping nature of the sub-circuits provides one explanation for the seamless orchestration by the embryo of cell state changes leading to successful EMT.
机译：上皮-间质转化（EMT）是一种基本的细胞状态改变，在胚胎发育，成人组织修复和癌症转移过程中，将上皮转化为间充质细胞。 EMT包括一系列复杂的中间细胞状态变化，包括基膜重塑，根尖收缩，上皮去粘连，定向运动，根尖基极丧失以及间充质粘连和极性的获得。转录调控状态的变化必须最终协调这些细胞生物学过程的时间安排和执行。海胆胚胎中一个特征明确的基因调控网络（GRN）用于鉴定在EMT过程中控制五个不同细胞变化的转录因子。单个转录因子受到干扰，其后果是通过体内延时成像或免疫染色测定法进行的。数据显示，GRN的五个不同子电路控制着五种不同的细胞生物学活性，这是复杂的EMT过程的每个部分。 EMT需要在EMT前细胞中特异性表达的13个转录因子（TF）。还需要GRN指定和激活的EMT中最高的三个TF（alx1，ets1，tbr）以及它们下游的10个TF（tel，erg，hex，tgif，蜗牛，twist，foxn2 / 3，dri，foxb，foxo）。用于EMT。在所有五个子电路中，没有单个TF起作用，表明没有EMT主调节器。相反，由此产生的子电路拓扑结构表明EMT需要多种同时的调节机制：正向级联，并行输入和正反馈锁定。子电路的相互连接和重叠性质为通过胚胎移植成功实现EMT的细胞状态变化的无缝编排提供了一种解释。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号