Epithelia can eliminate apoptotic cells by apical extrusion. This is a complex morphogenetic event where expulsion of the apoptotic cell is accompanied by rearrangement of its immediate neighbors to form a rosette. A key mechanism for extrusion is constriction of an actomyosin network that neighbor cells form at their interface with the apoptotic cell. Here we report a complementary process of cytoskeletal relaxation that occurs when cortical contractility is downregulated at the junctions between those neighbor cells themselves. This reflects a mechanosensitive Src family kinase (SFK) signaling pathway that is activated in neighbor cells when the apoptotic cell relaxes shortly after injury. Inhibiting SFK signaling blocks both the expulsion of apoptotic cells and rosette formation amongst their neighbor cells. This reveals the complex pattern of spatially-distinct contraction and relaxation that must be established in the neighboring epithelium for apoptotic cells to be extruded.

上皮细胞可以通过顶端挤出来消除凋亡细胞。这是一个复杂的形态发生事件，其中凋亡细胞的排出伴随着其紧邻细胞的重新排列以形成玫瑰花结。挤出的关键机制是相邻细胞在与凋亡细胞的界面处形成的肌动球蛋白网络的收缩。在这里，我们报告了当邻近细胞本身之间的连接处的皮质收缩性下调时发生的细胞骨架松弛的补充过程。这反映了当凋亡细胞在损伤后不久放松时，邻近细胞中的机械敏感性 Src 家族激酶 (SFK) 信号通路被激活。抑制 SFK 信号传导可阻止凋亡细胞的排出和邻近细胞之间玫瑰花结的形成。这揭示了空间上不同的收缩和松弛的复杂模式，这种模式必须在邻近的上皮细胞中建立，以便凋亡细胞被挤出。