The role of transcription factor dFoxO in regulating tracheal terminal cell plasticity of the fruit fly Drosophila melanogaster
Plasticity is a fundamental biological process that ensures that individuals' morphology, behavior, and physiology adapt to match their environment. Understanding the mechanisms that regulate trait plasticity is important because knowledge of how phenotypic plasticity is regulated has significant consequences for the study of diseases that result from changes in plasticity. Reduced O2 levels—or hypoxia, can lead to irreversible cellular damage in organisms, and therefore, organisms have evolved adaptive responses to compensate for the lack of O2. Drosophila melanogaster is highly resistant to oxygen deficiency and its respiratory (tracheal) system has features in common with the vertebrate vascular system. The tracheal terminal cells (TTCs) are plastic in nature, and they respond to hypoxia and different dietary conditions by sprouting out new branches, a process that can be compared to angiogenesis in mammals. Here we elucidate the role of the transcription factor, Forkhead box protein O(dFoxO) in regulating TTC plasticity. Deregulation of FoxO activity in the TTCs achieved by deficiency and overexpression of FoxO led to the loss of plasticity of the terminal cells. However, partial reduction of expression of FoxO via RNAi led to hyperbranching phenotype, suggesting that FoxO need to be expressed at a physiologically relevant level to maintain plasticity of the terminal cells. Suppressing JNK activity in the terminal cells did not affect the plasticity of the terminal cells, suggesting that the FoxO regulation in the terminal cells is independent of JNK activity. On the other hand, the induced release of Insulin from the insulin producing cells positively regulated the terminal branching, implying dFoxO might be regulated via IIS signaling.