Department of Entomology and MOA Lab for Pest Monitoring and Green Management, China Agricultural University, Beijing 100193, China.
Department of Entomology and MOA Lab for Pest Monitoring and Green Management, China Agricultural University, Beijing 100193, China
Development. 2020 Nov 17;147(22):dev190124. doi: 10.1242/dev.190124.
Cell extrusion is a crucial regulator of epithelial tissue development and homeostasis. Epithelial cells undergoing apoptosis, bearing pathological mutations or possessing developmental defects are actively extruded toward elimination. However, the molecular mechanisms of epithelial cell extrusion are not fully understood. Here, we report that activation of the conserved Hippo (Hpo) signaling pathway induces both apical and basal cell extrusion in the wing disc epithelia. We show that canonical Yorkie targets Diap1, Myc and Cyclin E are not required for either apical or basal cell extrusion induced by activation of this pathway. Another target gene, , is only involved in basal cell extrusion, suggesting novel Hpo-regulated apical cell extrusion mechanisms. Using RNA-seq analysis, we found that JNK signaling is activated in the extruding cells. We provide genetic evidence that JNK signaling activation is both sufficient and necessary for Hpo-regulated cell extrusion. Furthermore, we demonstrate that the ETS-domain transcription factor Ets21c, an ortholog of proto-oncogenes and , acts downstream of JNK signaling to mediate apical cell extrusion. Our findings reveal a novel molecular link between Hpo signaling and cell extrusion.
细胞挤出是上皮组织发育和稳态的关键调节因子。正在凋亡的上皮细胞、携带病理性突变或存在发育缺陷的上皮细胞会被主动挤出并消除。然而，上皮细胞挤出的分子机制尚不完全清楚。在这里，我们报告称，保守的 Hippo（Hpo）信号通路的激活会诱导 翅膀盘上皮细胞的顶端和基底细胞挤出。我们表明，经典的 Yorkie 靶标 Diap1、Myc 和 Cyclin E 既不需要也不参与该通路激活所诱导的顶端或基底细胞挤出。另一个靶基因 仅参与基底细胞挤出，这表明存在新的 Hpo 调控的顶端细胞挤出机制。通过 RNA-seq 分析，我们发现 JNK 信号在挤出的细胞中被激活。我们提供了遗传证据表明，JNK 信号的激活对于 Hpo 调控的细胞挤出既充分又必要。此外，我们证明 ETS 结构域转录因子 Ets21c，即原癌基因 和 的同源物，作为 JNK 信号的下游因子，介导顶端细胞挤出。我们的研究结果揭示了 Hpo 信号和细胞挤出之间的新的分子联系。
