Molecular integration of inductive and mesoderm-intrinsic inputs governs even-skipped enhancer activity in a subset of pericardial and dorsal muscle progenitors
Molecular integration of inductive and mesoderm-intrinsic inputs governs even-skipped enhancer activity in a subset of pericardial and dorsal muscle progenitors
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DOI：
10.1006/dbio.2001.0397
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发表时间：
2001-10-01
影响因子：
2.7
通讯作者：
Frasch, M
中科院分区：
文献类型：
--
作者：
Knirr, S;Frasch, M
个体躯体肌肉和心脏祖细胞被指定在果蝇中胚层内的确定位置。同源框基因 Even-skipped (eve) 的表达识别了背侧中胚层中的一个特定细胞亚群，这些细胞产生特定的心包细胞和背侧体壁肌肉。遗传分析表明，这些细胞中 eve 的诱导涉及编码中胚层内在因子（例如 Tinman (Tin)）的基因的组合活动，以及主要源自外胚层的空间限制信号活动，特别是由 wingless (wg) 和 decapentaplegic (dpp) 编码的信号活动。在这里，我们展示了 Dpp 激活的 Smad 蛋白（磷酸化 Mad）在延长的发育期间共定位于表达 eve 的细胞中。我们进一步证明 eve 的中胚层活性增强子含有几个对于体内增强子活性至关重要的 Smad 和 Tin 结合位点。该增强子还包含许多 Wg 效应器穿山甲 (Pan/Lef-1) 的结合位点，这是增强子活性达到最高水平所必需的。然而，我们发现它们的主要功能是防止背侧中胚层的异位增强子活性。这表明，在缺乏 Wg 信号传导的情况下，Pan 结合可消除 Smads 和 Tin 在 eve 激活中的协同活性，而在接收 Wg 信号的细胞中，Pan 转化为促进 eve 诱导的共激活剂。总之，这些数据表明，eve 增强子通过中胚层固有调节剂 Tin 与 Dpp 和 Wg 信号效应器的组合结合，整合了多种调节途径。 (C) 2001 年学术出版社。
Individual somatic muscles and heart progenitors are specified at defined positions within the mesodermal layer of Drosophila. The expression of the homeobox gene even-skipped (eve) identifies one specific subset of cells in the dorsal mesoderm, which give rise to particular pericardial cells and dorsal body wall muscles. Genetic analysis has shown that the induction of eve in these cells involves the combined activities of genes encoding mesoderm-intrinsic factors, such as Tinman (Tin), and spatially restricted signaling activities that are largely derived from the ectoderm, particularly those encoded by wingless (wg) and decapentaplegic (dpp). Here we show that a Dpp-activated Smad protein, phosphorylated Mad, is colocalized in eve-expressing cells during an extended developmental period. We demonstrate further that a mesodermally active enhancer of eve contains several Smad and Tin binding sites that are essential for enhancer activity in vivo. This enhancer also contains a number of binding sites for the Wg-effector Pangolin (Pan/Lef-1), which are required for full levels of enhancer activity. However, we find that their main function is to prevent ectopic enhancer activity in the dorsal mesoderm. This suggests that, in the absence of Wg signaling, Pan binding serves to abrogate the synergistic activities of Smads and Tin in eve activation while, in cells that receive Wg signals, Pan is converted into a coactivator that promotes eve induction. Together, these data show that the eve enhancer integrates several regulatory pathways via the combinatorial binding of the mesoderm-intrinsic regulator Tin and the effectors of the Dpp and Wg signals. (C) 2001 Academic Press.