The Francis Crick Institute, London, NW1 1AT, UK.
The Francis Crick Institute, London, NW1 1AT, UK.
Exp Cell Res. 2019 Aug 1;381(1):57-65. doi: 10.1016/j.yexcr.2019.04.040. Epub 2019 May 7.
Eph receptor and ephrin signaling has a major role in segregating distinct cell populations to form sharp borders. Expression of interacting Ephs and ephrins typically occurs in complementary regions, such that polarised activation of both components occurs at the interface. Forward signaling through Eph receptors can drive cell segregation, but it is unclear whether reverse signaling through ephrins can also contribute. We have tested the role of reverse signaling, and of polarised versus non-polarised activation, in assays in which contact repulsion drives cell segregation and border sharpening. We find that polarised forward signaling drives stronger segregation than polarised reverse signaling. Nevertheless, reverse signaling contributes since bidirectional Eph and ephrin activation drives stronger segregation than unidirectional forward signaling alone. In contrast, non-polarised Eph activation drives little segregation. We propose that although polarised forward signaling is the principal driver of segregation, reverse signaling enables bidirectional repulsion which prevents mingling of each population into the other.
Eph 受体和 Ephrin 信号在分隔不同细胞群体以形成清晰边界方面起着重要作用。相互作用的 Eph 和 Ephrin 的表达通常发生在互补区域，使得两个成分的极化激活都发生在界面上。Eph 受体的正向信号传导可以驱动细胞分离，但 Ephrin 的反向信号传导是否也能起到作用还不清楚。我们已经测试了反向信号传导以及极化与非极化激活在接触排斥驱动细胞分离和边界变锐的测定中的作用。我们发现，极化的正向信号传导比极化的反向信号传导驱动更强的分离。然而，反向信号传导是有贡献的，因为双向 Eph 和 Ephrin 的激活比单向正向信号传导单独作用驱动更强的分离。相比之下，非极化 Eph 的激活几乎不会引起细胞分离。我们提出，尽管极化的正向信号传导是分离的主要驱动因素，但反向信号传导能够双向排斥，防止每个群体混入另一个群体。
