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机械梯度驱动形态发生素噪声校正以确保稳健的图案形成。

Mechano-gradients drive morphogen-noise correction to ensure robust patterning.

机构信息

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.

出版信息

Sci Adv. 2024 Nov 15;10(46):eadp2357. doi: 10.1126/sciadv.adp2357.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d6/11567007/0a263478298b/sciadv.adp2357-f1.jpg

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