Laboratory of Behavioral and Developmental Genetics, Department of Human Genetics, KU Leuven-University of Leuven, Herestraat 49, Box 602, B-3000 Leuven, Belgium.
Laboratory of Behavioral and Developmental Genetics, Department of Human Genetics, KU Leuven-University of Leuven, Herestraat 49, Box 602, B-3000 Leuven, Belgium
Development. 2018 Nov 2;145(21):dev165654. doi: 10.1242/dev.165654.
Growth and maturation are coordinated processes in all animals. Integration of internal cues, such as signalling pathways, with external cues, such as nutritional status, is paramount for an orderly progression of development and growth. In , this involves insulin and steroid signalling, but the underlying mechanisms and their coordination are incompletely understood. We show that bioactive 20-hydroxyecdysone production by the enzyme Shade in the fat body is a nutrient-dependent process. We demonstrate that under fed conditions, Shade plays a role in growth control. We identify the trachea and the insulin-producing cells in the brain as direct targets through which 20-hydroxyecdysone regulates insulin signalling. The identification of trachea-dependent regulation of insulin signalling exposes an important variable that may have been overlooked in other studies focusing on insulin signalling in Our findings provide a potentially conserved, novel mechanism by which nutrition can modulate steroid hormone bioactivation, reveal an important caveat of a commonly used transgenic tool to study insulin-producing cell function, and yield further insights into how steroid and insulin signalling are coordinated during development to regulate growth and developmental timing.
在所有动物中,生长和成熟是协调的过程。内部线索(如信号通路)与外部线索(如营养状况)的整合对于有序的发育和生长至关重要。在这种情况下,涉及胰岛素和类固醇信号,但潜在的机制及其协调尚不完全清楚。我们表明,脂肪体中的酶 Shade 产生生物活性 20-羟基蜕皮甾酮是一个依赖营养的过程。我们证明,在进食条件下,Shade 在生长控制中发挥作用。我们确定气管和大脑中产生胰岛素的细胞是 20-羟基蜕皮甾酮调节胰岛素信号的直接靶标。气管依赖性胰岛素信号调节的鉴定揭示了一个重要的变量,在其他专注于胰岛素信号的研究中可能被忽视了。我们的发现提供了一种潜在保守的新机制,说明营养可以调节类固醇激素生物活化,揭示了一种常用的转基因工具在研究胰岛素产生细胞功能时的一个重要注意事项,并进一步深入了解类固醇和胰岛素信号在发育过程中如何协调以调节生长和发育时间。