Department of Homeostatic Regulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Fukuoka, Fukuoka 812-0054, Japan.
Sci Adv. 2024 Nov 15;10(46):eadp2357. doi: 10.1126/sciadv.adp2357.
Morphogen gradients instruct cells to pattern tissues. Although the mechanisms by which morphogens transduce chemical signals have been extensively studied, the roles and regulation of the physical communication between morphogen-receiver cells remain unclear. Here, we show that the Wnt/β-catenin-morphogen gradient, which patterns the embryonic anterior-posterior (AP) axis, generates intercellular tension gradients along the AP axis by controlling membrane cadherin levels in zebrafish embryos. This "mechano-gradient" is used for the cell competition-driven correction of noisy morphogen gradients. Naturally and artificially generated unfit cells, producing noisy Wnt/β-catenin gradients, induce local deformation of the mechano-gradients that activate mechanosensitive calcium channels in the neighboring fit cells, which then secrete annexin A1a to kill unfit cells. Thus, chemo-mechanical interconversion-mediated competitive communication between the morphogen-receiver cells ensures precise tissue patterning.
形态发生梯度指导细胞组织模式化。尽管形态发生素转导化学信号的机制已被广泛研究,但形态发生素-受体细胞之间物理通信的作用和调节仍不清楚。在这里,我们表明,Wnt/β-catenin 形态发生素梯度在斑马鱼胚胎中通过控制细胞膜钙粘蛋白水平来沿 AP 轴产生细胞间张力梯度,从而对胚胎前后(AP)轴进行模式化。这种“力学梯度”用于细胞竞争驱动的噪声形态发生素梯度的校正。自然产生和人为产生的不适应细胞产生嘈杂的 Wnt/β-catenin 梯度,会导致力学梯度的局部变形,从而激活相邻适应细胞中的机械敏感钙通道,然后这些适应细胞分泌 annexin A1a 杀死不适应细胞。因此,形态发生素-受体细胞之间的化学-机械转换介导的竞争通讯确保了精确的组织模式化。