Correcting developmental errors by apoptosis: lessons from Drosophila JNK signaling
Correcting developmental errors by apoptosis: lessons from Drosophila JNK signaling
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DOI：
10.1007/s10495-009-0361-7
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发表时间：
2009-08-01
期刊：
影响因子：
7.2
通讯作者：
Igaki, Tatsushi
中科院分区：
文献类型：
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作者：
Igaki, Tatsushi
细胞死亡机制的时空调控对于多细胞生物的正常发育和稳态是必不可少的。虽然由半胱天冬酶驱动的中央细胞死亡机制的分子基础现在已经有了很好的记录，但其调控机制，特别是在活体动物的背景下，仍有待澄清。c-Jun N-末端激酶（JNK）途径是调节凋亡机制的进化上保守的激酶级联。在哺乳动物中，JNK信号转导与应激诱导的细胞凋亡有关。果蝇遗传学现在提供了JNK介导的细胞死亡信号在消除组织中发育异常细胞的新作用的证据。JNK依赖性细胞消除系统由正常细胞和异常细胞之间的细胞间通讯协调，对于确保发育稳健性以及保护生物体免受致命异常（如肿瘤发育）至关重要。这些过程由细胞竞争、形态发生凋亡和内在肿瘤抑制介导。在果蝇中使用遗传和实时成像系统的组合方法将非常强大，以破译JNK介导的细胞凋亡在多细胞群落中的作用。
Spatio-temporal regulation of the cell death machinery is essential for normal development and homeostasis of multicellular organisms. While the molecular basis for the central cell death machinery driven by caspases is now well documented, its regulatory mechanisms, especially in the context of living animals, remain to be clarified. The c-Jun N-terminal kinase (JNK) pathway is an evolutionarily conserved kinase cascade that regulates the apoptotic machinery. In mammals, JNK signaling has been implicated in stress-induced apoptosis. Drosophila genetics has now provided evidence of a novel role for JNK-mediated cell death signaling in eliminating developmentally aberrant cells from a tissue. The JNK-dependent cell-elimination system is orchestrated by cell-cell communication between normal and aberrant cells and is essential for ensuring developmental robustness, as well as for protecting organisms against fatal abnormalities such as neoplastic development. These processes are mediated by cell competition, morphogenetic apoptosis, and intrinsic tumor suppression. A combinatorial approach using both genetic and live-imaging systems in Drosophila will be extremely powerful to decipher how JNK-mediated apoptosis works within multicellular communities.