Limited role of developmental programmed cell death pathways in Drosophila norpA retinal degeneration
Limited role of developmental programmed cell death pathways in Drosophila norpA retinal degeneration
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DOI：
10.1523/jneurosci.3328-02.2004
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发表时间：
2004-01-14
影响因子：
5.3
通讯作者：
O'Tousa, JE
中科院分区：
文献类型：
--
作者：
Hsu, CD;Whaley, MA;O'Tousa, JE
我们研究了程序性细胞死亡(PCD)通路在Norpa基因突变引起的视网膜变性中的作用。Norpa变性表现出细胞程序性死亡的形态特征，特别是细胞质凝聚和被邻近的视网膜色素细胞吞噬死亡的光感受器细胞。然而，缺乏RPR、HID和GRIM的成年光感受器的遗传镶嵌分析表明，这些PCD诱导剂不是Norpa退化所必需的。我们以前已经证明，RPR或HID的异位表达在成体光感受器中触发快速PCD，而这一过程完全被杆状病毒P35半胱氨酸酶抑制剂的共同表达所抑制。相反，P35的表达并不抑制Norpa视网膜的退化，尽管在弱光-低温条件下观察到退化速度的微小延迟。P35不改变Norpa细胞死亡的形态特征。果蝇凋亡抑制因子Diap1或Dronc caspase的显性阴性形式的过表达，即使与P35共表达，也不会显著改变Norpa变性的时间进程。这些结果表明，在由Norpa引起的成人视网膜变性中，在发育过程中负责PCD的途径并不起主要作用。
We examined the role of programmed cell death (PCD) pathways in retinal degeneration caused by a mutation in the norpA gene. norpA degeneration shows morphological hallmarks of programmed cell death, specifically cytoplasmic condensation and engulfment of the dying photoreceptor cells by neighboring retinal pigment cells. However, genetic mosaic analysis of adult photoreceptors lacking rpr, hid, and grim show that these PCD inducers are not required for norpA degeneration. We showed previously that ectopic expression of either rpr or hid triggers rapid PCD in adult photoreceptors, and this is completely suppressed by the coexpression of the baculoviral P35 caspase inhibitor. In contrast, expression of P35 does not suppress norpA retinal degeneration, although a small delay in the rate of degeneration is observed in low light-low temperature conditions. P35 does not alter the morphological characteristics of norpA cell death. Overexpression of the Drosophila inhibitor of apoptosis Diap1 or a dominant-negative form of the Dronc caspase, even when coexpressed with P35, does not dramatically alter the time course of norpA degeneration. These results establish that the pathways responsible for PCD in development do not play a major role in adult retinal degeneration caused by norpA.