Javaherian Sahar, D'Arcangelo Elisa, Slater Benjamin, Londono Camila, Xu Bin, McGuigan Alison P
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College St., Toronto, ON M5S 3E5, Canada.
Integr Biol (Camb). 2017 Dec 11;9(12):934-946. doi: 10.1039/c7ib00176b.
Compartment boundaries are essential for ensuring proper cell organization during embryo development and in adult tissues, yet the mechanisms underlying boundary establishment are not completely understood. A number of mechanisms, including (i) differential adhesion, (ii) differential tension, and (iii) cell signaling-mediated cell repulsion, are known to contribute and likely a context-dependent balance of each of these dictates boundary implementation. The ephrin/Eph signaling pathway is known to impact boundary formation in higher animals. In different contexts, ephrin/Eph signaling is known to modulate adhesive properties and migratory behavior of cells. Furthermore it has been proposed that ephrin/Eph signaling may modulate cellular tensile properties, leading to boundary implementation. It remains unclear however, whether, in different contexts, ephrin/Eph act through distinct dominant action modes (e.g. differential adhesion vs. cell repulsion), or whether ephrin/Eph signaling elicits multiple cellular changes simultaneously. Here, using micropatterning of cells over-expressing either EphB3 or ephrinB1, we assess the contribution of each these factors in one model. We show that in this system ephrinB1/EphB3-mediated boundaries are accompanied by modulation of tissue-level architecture and polarization of cell migration. These changes are associated with changes in cell shape and cytoskeletal organization also suggestive of altered cellular tension.
在胚胎发育和成年组织中，隔室边界对于确保细胞的正确组织至关重要，然而边界形成的潜在机制尚未完全了解。已知多种机制，包括（i）差异黏附、（ii）差异张力和（iii）细胞信号介导的细胞排斥，都对边界形成有贡献，并且这些机制可能在不同情况下相互平衡，从而决定边界的形成。已知 Ephrin/Eph 信号通路会影响高等动物的边界形成。在不同情况下，Ephrin/Eph 信号通路已知会调节细胞的黏附特性和迁移行为。此外，有人提出 Ephrin/Eph 信号通路可能会调节细胞的拉伸特性，从而导致边界的形成。然而，目前尚不清楚在不同情况下，Ephrin/Eph 是否通过不同的主导作用模式（例如差异黏附与细胞排斥）起作用，或者 Ephrin/Eph 信号通路是否会同时引发多种细胞变化。在这里，我们通过对过表达 EphB3 或 ephrinB1 的细胞进行微图案化处理，在一个模型中评估了这些因素各自的作用。我们表明，在这个系统中，ephrinB1/EphB3 介导的边界伴随着组织水平结构的调节和细胞迁移的极化。这些变化与细胞形状和细胞骨架组织的变化相关，也表明细胞张力发生了改变。
