Epigenetically heritable alteration of fly development in response to toxic challenge . Drosophila melanogaster

Developing organisms have evolved a wide range of mechanisms for coping with recurrent environmental challenges. How they cope with rare or unforeseen challenges is, however, unclear as are the implications to their unchallenged offspring. Here we investigate these questions by confronting the development of the fly, D. melanogaster, with artificial tissue distributions of toxic stress that are not expected to occur during fly development. We show that under a wide range of toxic scenarios, this challenge can lead to modified development which may coincide with increased tolerance to an otherwise lethal condition. Part of this response was mediated by suppression of Polycomb group genes, which in turn leads to de-repression of developmental regulators and their expression in new domains. Importantly, some of the developmental alterations were epigenetically inherited by subsequent generations of unchallenged offspring. These results show that the environment can induce alternative patterns of development that are stable across multiple generations. Overall design: Measuring differences in RNA levels between larvae that were exposed to a toxic challenge and unchallenged larvae. measuring differences in RNA levels between F3 larvae with or without past exposure to the challenge in F1 generation.

发育中的生物体已演化出多种机制以应对反复出现的环境挑战。然而，生物体如何应对罕见或突发的环境挑战，以及此类挑战对其未受挑战的后代的影响，目前仍不明确。
本研究以黑腹果蝇（D. melanogaster）为研究对象，通过施加其发育过程中不会自然出现的人工组织毒性应激分布，对上述问题展开探究。
我们发现，在多种毒性应激情境下，此类挑战可引发发育模式改变，同时伴随对原本致死性刺激的耐受性提升。
该应答的一部分由多梳蛋白家族基因（Polycomb group genes）的抑制所介导，进而解除发育调控因子的转录抑制，并使其在新的组织区域中表达。
值得注意的是，部分发育改变可通过表观遗传方式传递给后续未受挑战的子代世代。
上述结果表明，环境可诱导出可在多代间稳定传递的替代性发育模式。
实验设计：分别检测暴露于毒性应激的幼虫与未受挑战幼虫的RNA水平差异；同时检测F1代曾暴露于该应激的F3代幼虫与未经历过该应激的F3代幼虫的RNA水平差异。