Phagocytosis genes nonautonomously promote developmental cell death in the Drosophila ovary

Phagocytosis genes nonautonomously promote developmental cell death in the Drosophila ovary
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DOI:
10.1073/pnas.1522830113
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发表时间:
2016-03-01
影响因子:
11.1
通讯作者:
McCall, Kimberly
McCall, Kimberly
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Timmons, Allison K.;Mondragon, Albert A.;McCall, Kimberly

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程序性细胞死亡(PCD)通常被认为是一种细胞自主自杀程序,与细胞凋亡同义。最近的研究表明,PCD是复杂的,至少有十几种细胞死亡方式。在这里,我们证明了果蝇卵巢中大规模的非凋亡性发育性PCD是通过一种替代细胞死亡程序发生的,其中周围的卵泡细胞非自主地促进了生殖系的死亡。卵泡细胞的吞噬机制,包括Draper、细胞死亡异常(Ced)-12和c-Jun n -末端激酶(JNK),对于生殖系来源的哺乳细胞在卵子发生后期的死亡和移除至关重要。当吞噬作用被抑制时,细胞死亡事件包括酸化、核膜渗透和护理细胞的DNA断裂。此外,消除一小部分卵泡细胞可防止护理细胞死亡和细胞质倾倒。果蝇卵巢的发育性PCD是非凋亡性、非自主性PCD的一个有趣例子,为细胞死亡机制的多样性提供了见解。
Programmed cell death (PCD) is usually considered a cell-autonomous suicide program, synonymous with apoptosis. Recent research has revealed that PCD is complex, with at least a dozen cell death modalities. Here, we demonstrate that the large-scale nonapoptotic developmental PCD in the Drosophila ovary occurs by an alternative cell death program where the surrounding follicle cells nonautonomously promote death of the germ line. The phagocytic machinery of the follicle cells, including Draper, cell death abnormality (Ced)-12, and c-Jun N-terminal kinase (JNK), is essential for the death and removal of germ-line-derived nurse cells during late oogenesis. Cell death events including acidification, nuclear envelope permeabilization, and DNA fragmentation of the nurse cells are impaired when phagocytosis is inhibited. Moreover, elimination of a small subset of follicle cells prevents nurse cell death and cytoplasmic dumping. Developmental PCD in the Drosophila ovary is an intriguing example of nonapoptotic, nonautonomous PCD, providing insight on the diversity of cell death mechanisms.