Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore, India.
SASTRA University, Thirumalaisamudram, India.
Elife. 2020 Sep 2;9:e57056. doi: 10.7554/eLife.57056.
Larval tracheae of harbour progenitors of the adult tracheal system (tracheoblasts). Thoracic tracheoblasts are arrested in the G2 phase of the cell cycle in an ATR (mei-41)-Checkpoint Kinase1 (grapes, Chk1) dependent manner prior to mitotic re-entry. Here we investigate developmental regulation of Chk1 activation. We report that Wnt signaling is high in tracheoblasts and this is necessary for high levels of activated (phosphorylated) Chk1. We find that canonical Wnt signaling facilitates this by transcriptional upregulation of Chk1 expression in cells that have ATR kinase activity. Wnt signaling is dependent on four Wnts (Wg, Wnt5, 6,10) that are expressed at high levels in arrested tracheoblasts and are downregulated at mitotic re-entry. Interestingly, none of the Wnts are dispensable and act synergistically to induce Chk1. Finally, we show that downregulation of Wnt signaling and Chk1 expression leads to mitotic re-entry and the concomitant upregulation of Dpp signaling, driving tracheoblast proliferation.
幼虫气管的港口的成年气管系统的祖细胞（tracheoblasts）。在有丝分裂重新进入之前，胸tracheoblasts 以 ATR（mei-41）-检查点激酶 1（grapes，Chk1）依赖性方式在细胞周期的 G2 期停滞。在这里，我们研究了 Chk1 激活的发育调节。我们报告说，Wnt 信号在 tracheoblasts 中很高，这对于高水平的激活（磷酸化）Chk1 是必要的。我们发现，经典的 Wnt 信号通过在具有 ATR 激酶活性的细胞中转录上调 Chk1 表达来促进这种作用。Wnt 信号依赖于四种 Wnts（Wg、Wnt5、6、10），它们在被阻止的气管细胞中高水平表达，并在有丝分裂重新进入时下调。有趣的是，没有一个 Wnts 是可有可无的，它们协同作用诱导 Chk1。最后，我们表明下调 Wnt 信号和 Chk1 表达导致有丝分裂重新进入，同时上调 Dpp 信号，驱动 tracheoblast 增殖。
