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Wnt/β-连环蛋白信号传导诱导细胞外基质的轴向弹性模式。

Wnt/β-catenin signaling induces axial elasticity patterns of extracellular matrix.

作者信息

Veschgini Mariam, Suzuki Ryo, Kling Svenja, Petersen Hendrik O, Bergheim Bruno Gideon, Abuillan Wasim, Linke Philipp, Kaufmann Stefan, Burghammer Manfred, Engel Ulrike, Stein Frank, Özbek Suat, Holstein Thomas W, Tanaka Motomu

机构信息

Physical Chemistry of Biosystems, Institute of Physical Chemistry, Heidelberg University, D69120 Heidelberg, Germany.

Center for Integrated Medicine and Physics, Institute for Advanced Study, Kyoto University, Kyoto 606-8501, Japan.

出版信息

iScience. 2023 Mar 16;26(4):106416. doi: 10.1016/j.isci.2023.106416. eCollection 2023 Apr 21.

Abstract

The extracellular matrix (ECM) plays crucial roles in animal development and diseases. Here, we report that Wnt/β-catenin signaling induces the ECM remodeling during axis formation. We determined the micro- and nanoscopic arrangement of fibrillar type I collagen along body axis using high-resolution microscopy and X-ray scattering. Elasticity mapping of the ECM revealed distinctive elasticity patterns along the body axis. A proteomic analysis of the ECM showed that these elasticity patterns correlate with a gradient-like distribution of metalloproteases along the body axis. Activation of the Wnt/β-catenin pathway in wild-type and transgenic animals alters these patterns toward low ECM elasticity patterns. This suggests a mechanism whereby high protease activity under control of Wnt/β-catenin signaling causes remodeling and softening of the ECM. This Wnt-dependent spatiotemporal coordination of biochemical and biomechanical cues in ECM formation was likely a central evolutionary innovation for animal tissue morphogenesis.

摘要

细胞外基质(ECM)在动物发育和疾病中发挥着关键作用。在此,我们报告Wnt/β-连环蛋白信号通路在轴形成过程中诱导细胞外基质重塑。我们使用高分辨率显微镜和X射线散射确定了沿身体轴的纤维状I型胶原蛋白的微观和纳米级排列。细胞外基质的弹性图谱揭示了沿身体轴的独特弹性模式。对细胞外基质的蛋白质组学分析表明,这些弹性模式与金属蛋白酶沿身体轴的梯度样分布相关。野生型和转基因动物中Wnt/β-连环蛋白通路的激活将这些模式改变为低细胞外基质弹性模式。这提示了一种机制,即Wnt/β-连环蛋白信号通路控制下的高蛋白酶活性导致细胞外基质的重塑和软化。细胞外基质形成中这种依赖Wnt的生化和生物力学信号的时空协调可能是动物组织形态发生的一项核心进化创新。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1507/10050647/cefe7d82ec63/fx1.jpg

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