Laboratory for Morphogenetic Signaling, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Department of Biology, Kobe University Graduate School of Science, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8051, Japan.
Development. 2023 Mar 1;150(5). doi: 10.1242/dev.201231. Epub 2023 Mar 9.
Dying cells in the epithelia communicate with neighboring cells to initiate coordinated cell removal to maintain epithelial integrity. Naturally occurring apoptotic cells are mostly extruded basally and engulfed by macrophages. Here, we have investigated the role of Epidermal growth factor (EGF) receptor (EGFR) signaling in the maintenance of epithelial homeostasis. In Drosophila embryos, epithelial tissues undergoing groove formation preferentially enhanced extracellular signal-regulated kinase (ERK) signaling. In EGFR mutant embryos at stage 11, sporadic apical cell extrusion in the head initiates a cascade of apical extrusions of apoptotic and non-apoptotic cells that sweeps the entire ventral body wall. Here, we show that this process is apoptosis dependent, and clustered apoptosis, groove formation, and wounding sensitize EGFR mutant epithelia to initiate massive tissue disintegration. We further show that tissue detachment from the vitelline membrane, which frequently occurs during morphogenetic processes, is a key trigger for the EGFR mutant phenotype. These findings indicate that, in addition to cell survival, EGFR plays a role in maintaining epithelial integrity, which is essential for protecting tissues from transient instability caused by morphogenetic movement and damage.
上皮细胞中的死亡细胞与邻近细胞通讯，启动协调的细胞清除，以维持上皮完整性。天然发生的凋亡细胞大多从基底侧挤出并被巨噬细胞吞噬。在这里，我们研究了表皮生长因子 (EGF) 受体 (EGFR) 信号在维持上皮稳态中的作用。在果蝇胚胎中，形成沟的上皮组织优先增强细胞外信号调节激酶 (ERK) 信号。在第 11 阶段的 EGFR 突变体胚胎中，头部散在的顶端细胞挤出启动一连串的顶端挤出凋亡和非凋亡细胞，席卷整个腹侧体壁。在这里，我们表明这个过程是依赖凋亡的，并且凋亡聚集、沟形成和创伤使 EGFR 突变体上皮细胞容易启动大量的组织解体。我们进一步表明，从卵黄膜上的组织分离，这在形态发生过程中经常发生，是 EGFR 突变体表型的一个关键触发因素。这些发现表明，除了细胞存活外，EGFR 在维持上皮完整性方面也发挥作用，这对于保护组织免受形态发生运动和损伤引起的短暂不稳定至关重要。
