School of Biology, Indian Institute of Science Education and Research (IISER TVM), Maruthamala Post, Vithura, Thiruvananthapuram, Kerala 695551, India.
Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108 Freiburg im Breisgau, Germany.
Genetics. 2021 May 17;218(1). doi: 10.1093/genetics/iyab035.
Insulin signaling in Drosophila has a significant role in regulating growth, metabolism, fecundity, stress response, and longevity. The molecular mechanism by which insulin signaling regulates these vital processes is dependent on the nutrient status and oxygen availability of the organism. In a genetic screen to identify novel genes that regulate Drosophila insulin signaling, we discovered lumens interrupted (lint), a gene that has previously been shown to act in tracheal development. The knockdown of lint gene expression using a Dilp2Gal4 driver which expresses in the neuronal insulin producing cells (IPCs), led to defects in systemic insulin signaling, metabolic status and growth. However, our analysis of lint knockdown phenotypes revealed that downregulation of lint in the trachea and not IPCs was responsible for the growth phenotypes, as the Gal4 driver is also expressed in the tracheal system. We found various tracheal terminal branch defects, including reduction in the length as well as number of branches in the lint knockdown background. Our study reveals that substantial effects of lint downregulation arose because of tracheal defects, which induced tissue hypoxia, altered systemic insulin/TOR signaling, and resulted in effects on developmental growth regulation.
在果蝇中，胰岛素信号在调节生长、代谢、繁殖力、应激反应和寿命方面起着重要作用。胰岛素信号调节这些重要过程的分子机制依赖于生物体的营养状态和氧气供应。在一项旨在鉴定调控果蝇胰岛素信号的新基因的遗传筛选中，我们发现了 lumen interrupted（lint），这是一个先前被证明在气管发育中起作用的基因。使用 Dilp2Gal4 驱动子（在神经元胰岛素产生细胞（IPCs）中表达）敲低 lint 基因表达，导致系统性胰岛素信号、代谢状态和生长缺陷。然而，我们对 lint 敲低表型的分析表明，气管而不是 IPCs 中 lint 的下调是导致生长表型的原因，因为 Gal4 驱动子也在气管系统中表达。我们发现了各种气管末端分支缺陷，包括 lint 敲低背景下分支长度和数量的减少。我们的研究表明，lint 下调的实质性影响是由于气管缺陷引起的，这些缺陷导致组织缺氧，改变了系统性胰岛素/TOR 信号，并对发育生长调节产生了影响。
