Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Department of Obstetrics Gynecology and Reproductive Biology, and Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI 48824, USA.
Sci Adv. 2024 Jul 19;10(29):eadl6366. doi: 10.1126/sciadv.adl6366.
Physical processes ultimately shape tissue during development. Two emerging proposals are that cells migrate toward stiffer tissue (durotaxis) and that the extent of cell rearrangements reflects tissue phase, but it is unclear whether and how these concepts are related. Here, we identify fibronectin-dependent tissue stiffness as a control variable that underlies and unifies these phenomena in vivo. In murine limb bud mesoderm, cells are either caged, move directionally, or intercalate as a function of their location along a stiffness gradient. A modified Landau phase equation that incorporates tissue stiffness accurately predicts cell diffusivity upon loss or gain of fibronectin. Fibronectin is regulated by WNT5A-YAP feedback that controls cell movements, tissue shape, and skeletal pattern. The results identify a key determinant of phase transition and show how fibronectin-dependent directional cell movement emerges in a mixed-phase environment in vivo.
物理过程最终在发育过程中塑造组织。有两个新兴的观点是，细胞向更硬的组织迁移（趋硬性），以及细胞重排的程度反映了组织的相位，但尚不清楚这些概念是否以及如何相关。在这里，我们确定纤维连接蛋白依赖性组织硬度是一个控制变量，它在体内是这些现象的基础和统一。在鼠肢芽中胚层中，细胞被笼养、定向移动或相互穿插，这取决于它们在硬度梯度上的位置。一个改进的朗道相方程，将组织硬度纳入其中，可以准确预测纤维连接蛋白缺失或获得时细胞的扩散率。纤维连接蛋白受 WNT5A-YAP 反馈调节，控制细胞运动、组织形状和骨骼模式。结果确定了相变的关键决定因素，并展示了纤维连接蛋白依赖性定向细胞运动如何在体内混合相环境中出现。
