E-cadherin prolongs the moment for interaction between intestinal stem cell and its progenitor cell to ensure Notch signaling in adult Drosophila midgut
E-cadherin prolongs the moment for interaction between intestinal stem cell and its progenitor cell to ensure Notch signaling in adult Drosophila midgut
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DOI：
10.1111/j.1365-2443.2008.01239.x
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发表时间：
2008-12-01
期刊：
影响因子：
2.1
通讯作者：
Adachi-Yamada, Takashi
中科院分区：
文献类型：
--
作者：
Maeda, Kousuke;Takemura, Masahiko;Adachi-Yamada, Takashi
肠干细胞（ISCs）是维持成人肠道中适当细胞组成所必需的。为了确保新分化细胞的永久招募，ISC经历不对称细胞分裂，产生ISC本身和祖细胞。在果蝇中肠中，吸收细胞的命运是由祖细胞中的Notch (N)信号决定的，祖细胞接受由ISCs产生的配体Delta （Dl）。虽然大多数ISCs和祖细胞位于较远的位置，但由于Dl-N相互作用需要细胞粘附，当N被激活时，它们应保持附着。此外，在细胞分裂完成之前，N不能被激活。因此，细胞分裂后和细胞分离前的时刻应该延长某些N激活，尽管其机制尚不清楚。在这里，我们证明了e -钙粘蛋白（E-cad）是两个细胞之间稳定附着所必需的。当E-cad不起作用时，N不被激活，细胞分化减弱。我们还表明，N失活的ISC肿瘤是由E-cad下调缺陷辅助的。这些发现揭示了通过降低E-cad来抑制肿瘤发生的正常N功能之一，以实现适当的中肠细胞周转。
Intestinal stem cells (ISCs) are required for maintenance of the proper cell composition in the adult intestine. To ensure permanent recruitment of newly differentiated cells, the ISC undergoes asymmetric cell division that generates an ISC itself and a progenitor cell. In the Drosophila midgut, cell fate for the absorptive cell is determined by Notch (N) signal in the progenitor cells that receive a ligand Delta (Dl) produced by the ISCs. Although most of the ISCs and progenitor cells are distantly located, they should retain their attachment when N is activated because the Dl-N interaction requires cell adhesion. Furthermore, N cannot be activated before completion of cell division. Thus, the moment after cell division and before cell separation should be prolonged for certain N activation, although the mechanism for this remains unclear. Here, we demonstrate that E-cadherin (E-cad) is required for stable attachment between the two cells. When E-cad does not function, N is not activated and cell differentiation is attenuated. We also show that the ISC tumor by N inactivation is assisted by a defect in E-cad down-regulation. These findings reveal one of the normal N functions used to inhibit tumorigenesis through lowering of E-cad for proper midgut cell turnover.