Department of Biology, Boston University, Boston, MA 02215, USA.
Development. 2012 Nov;139(21):4029-39. doi: 10.1242/dev.082776. Epub 2012 Sep 19.
The efficient removal of dead cells is an important process in animal development and homeostasis. Cell corpses are often engulfed by professional phagocytes such as macrophages. However, in some tissues with limited accessibility to circulating cells, engulfment is carried out by neighboring non-professional phagocytes such as epithelial cells. Here, we investigate the mechanism of corpse clearance in the Drosophila melanogaster ovary, a tissue that is closed to circulating cells. In degenerating egg chambers, dying germline cells are engulfed by the surrounding somatic follicular epithelium by unknown mechanisms. We show that the JNK pathway is activated and required in engulfing follicle cells. We find that the receptor Draper is also required in engulfing follicle cells, and activates the JNK pathway. Overexpression of Draper or the JNK pathway in follicle cells is sufficient to induce death of the underlying germline, suggesting that there is coordination between the germline and follicular epithelium to promote germline cell death. Furthermore, activation of JNK bypasses the need for Draper in engulfment. The induction of JNK and Draper in follicle cells occurs independently of caspase activity in the germline, indicating that at least two pathways are necessary to coordinate germline cell death with engulfment by the somatic epithelium.
细胞死亡的有效清除是动物发育和内稳态过程中的一个重要过程。细胞尸体通常被专业吞噬细胞如巨噬细胞吞噬。然而，在一些循环细胞难以进入的组织中，吞噬作用是由邻近的非专业吞噬细胞如上皮细胞完成的。在这里，我们研究了果蝇卵巢中细胞尸体清除的机制，该组织与循环细胞隔离。在退化的卵囊中，死亡的生殖细胞通过未知的机制被周围的体细胞滤泡上皮细胞吞噬。我们发现 JNK 途径在吞噬滤泡细胞中被激活并被需要。我们发现 Draper 受体在吞噬滤泡细胞中也被需要，并激活 JNK 途径。在滤泡细胞中过表达 Draper 或 JNK 途径足以诱导下方生殖细胞的死亡，这表明生殖细胞和滤泡上皮细胞之间存在协调作用，以促进生殖细胞死亡。此外，JNK 的激活绕过了Draper 在吞噬作用中的需要。JNK 和 Draper 在滤泡细胞中的诱导独立于生殖细胞中的 Caspase 活性，这表明至少有两条途径是协调生殖细胞死亡与体细胞上皮细胞吞噬作用所必需的。
