Cap-n-Collar Promotes Tissue Regeneration by Regulating ROS and JNK Signaling in the Drosophila melanogaster Wing Imaginal Disc
Cap-n-Collar Promotes Tissue Regeneration by Regulating ROS and JNK Signaling in the Drosophila melanogaster Wing Imaginal Disc
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DOI：
10.1534/genetics.116.196832
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发表时间：
2017-07-01
期刊：
影响因子：
3.3
通讯作者：
Smith-Bolton, Rachel K.
中科院分区：
文献类型：
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作者：
Brock, Amanda R.;Seto, Mabel;Smith-Bolton, Rachel K.
再生是一个复杂的过程，需要有机体识别和修复组织损伤，以及生长和形成新组织。在这里，我们描述了一种遗传筛选来识别新的再生调节因子。我们通过以空间和时间控制的方式诱导细胞凋亡来消除果蝇幼虫翅膀原基，并允许组织再生和重新模式化。为了鉴定调节再生的基因，我们通过评估同基因缺陷杂合的成年翅膀的再生数量和质量来进行显性修饰筛选。我们已经确定了第三染色体右臂上的 31 个区域可以改变再生反应。有趣的是，我们观察到了几种不同的表型：再生不良的突变体、比野生型再生更快或更好的突变体、以及再生不完美且具有图案缺陷的突变体。我们将一个缺陷区域映射到 cap-n-collar (cnc)，果蝇 Nrf2 直系同源物，这是再生所需的。 Cnc 调节再生上皮中的活性氧水平，并影响 c-Jun N 末端蛋白激酶 (JNK) 信号传导、生长、碎片定位和化蛹时间。在这里，我们展示了我们的筛选结果，并提出了一个模型，其中 Cnc 通过维持活性氧的最佳水平来促进 JNK 信号传导来调节再生。
Regeneration is a complex process that requires an organism to recognize and repair tissue damage, as well as grow and pattern new tissue. Here, we describe a genetic screen to identify novel regulators of regeneration. We ablated the Drosophila melanogaster larval wing primordium by inducing apoptosis in a spatially and temporally controlled manner and allowed the tissue to regenerate and repattern. To identify genes that regulate regeneration, we carried out a dominant-modifier screen by assessing the amount and quality of regeneration in adult wings heterozygous for isogenic deficiencies. We have identified 31 regions on the right arm of the third chromosome that modify the regenerative response. Interestingly, we observed several distinct phenotypes: mutants that regenerated poorly, mutants that regenerated faster or better than wild-type, and mutants that regenerated imperfectly and had patterning defects. We mapped one deficiency region to cap-n-collar (cnc), the Drosophila Nrf2 ortholog, which is required for regeneration. Cnc regulates reactive oxygen species levels in the regenerating epithelium, and affects c-Jun N-terminal protein kinase (JNK) signaling, growth, debris localization, and pupariation timing. Here, we present the results of our screen and propose a model wherein Cnc regulates regeneration by maintaining an optimal level of reactive oxygen species to promote JNK signaling.