Steroid regulation of midgut cell death during Drosophila development
Steroid regulation of midgut cell death during Drosophila development
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DOI：
10.1006/dbio.2002.0784
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发表时间：
2002-10-01
影响因子：
2.7
通讯作者：
Baehrecke, EH
中科院分区：
文献类型：
--
作者：
Lee, CY;Cooksey, BAK;Baehrecke, EH
类固醇激素通过激活细胞增殖、细胞分化和细胞死亡在动物发育期间触发动态组织变化。在这里，我们的特点类固醇调节果蝇变态的发病过程中肠结构的变化。在幼虫发育结束时类固醇20-羟基蜕皮激素（蜕皮激素）增加后，形成了未来的成虫中肠上皮，幼虫中肠迅速被破坏。类固醇调节基因BR-C和E93的突变对幼虫中肠细胞死亡的影响不同，但不影响成虫中肠上皮的形成。相反，蜕皮激素调控的E74 A和E74 B基因的突变似乎不会干扰变态过程中的中肠发育。幼虫中肠细胞具有含有细胞器的空泡，表明这些细胞通过自噬死亡。虽然BR-C、E74和E93基因的突变在这种细胞死亡过程中不影响DNA降解，但BR-C的突变抑制了幼虫中肠结构的破坏，包括前胃和胃盲囊，并且E93突变体表现出自噬空泡形成减少。死亡的中肠表达rpr，hid，方舟，dronc和crq细胞死亡基因，表明核心细胞死亡机制参与了幼虫中肠细胞死亡。在BR-C突变体中，rpr、hid和crq的转录发生改变，E93突变体具有半胱天冬酶dronc的转录改变，这为这些突变动物中肠细胞死亡的破坏提供了一种机制。这些研究表明，蜕皮激素触发了一个由类固醇诱导的调控基因和凋亡基因组成的两步层次结构，反过来，调节发育过程中肠细胞的自噬性死亡。(C)2002 Elsevier Science（美国）。
Steroid hormones trigger dynamic tissue changes during animal development by activating cell proliferation, cell differentiation, and cell death. Here we characterize steroid regulation of changes in midgut structure during the onset of Drosophila metamorphosis. Following an increase in the steroid 20-hydroxyecdysone (ecdysone) at the end of larval development, future adult midgut epithelium is formed, and the larval midgut is rapidly destroyed. Mutations in the steroid-regulated genes BR-C and E93 differentially impact larval midgut cell death but do not affect the formation of adult midgut epithelia. In contrast, mutations in the ecdysone-regulated E74A and E74B genes do not appear to perturb midgut development during metamorphosis. Larval midgut cells possess vacuoles that contain cellular organelles, indicating that these cells die by autophagy. While mutations in the BR-C, E74, and E93 genes do not impact DNA degradation during this cell death, mutations in BR-C inhibit destruction of larval midgut structures, including the proventriculus and gastric caeca, and E93 mutants exhibit decreased formation of autophagic vacuoles. Dying midguts express the rpr, hid, ark, dronc, and crq cell death genes, suggesting that the core cell death machinery is involved in larval midgut cell death. The transcription of rpr, hid, and crq are altered in BR-C mutants, and E93 mutants possess altered transcription of the caspase dronc, providing a mechanism for the disruption of midgut cell death in these mutant animals. These studies indicate that ecdysone triggers a two-step hierarchy composed of steroid-induced regulatory genes and apoptosis genes that, in turn, regulate the autophagic death of midgut cells during development. (C) 2002 Elsevier Science (USA).