Gaddelapati Sharath Chandra, Palli Subba Reddy
Department of Entomology, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, 40546, USA.
Department of Entomology, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, 40546, USA.
Insect Biochem Mol Biol. 2025 Feb;177:104256. doi: 10.1016/j.ibmb.2024.104256. Epub 2024 Dec 30.
Controlling Aedes aegypti mosquitoes is crucial for managing mosquito-transmitted diseases like dengue, zika, chikungunya, and yellow fever. One of the efficient methods to control mosquitoes is to block their progression from the larval to the adult stage. Juvenile hormones (JH) maintain the larval stage and ensure proper developmental timing for transitioning from larval-pupal-adult stages. Our previous studies showed that histone deacetylases (HDACs) regulate JH signaling and metamorphosis in the red flour beetle Tribolium castaneum. However, the role of HDACs in regulating JH signaling in Ae. aegypti mosquito is unknown. To investigate the role of HDACs in JH signaling, we knockdown each HDAC coding gene in Aag-2 cells derived from Ae. aegypti. Knockdown of HDAC1, HDAC4, and HDAC11 increased the expression of the JH primary response gene, Krüppel homolog 1 (Kr-h1), which represses the larval-pupal metamorphosis. Moreover, the simultaneous knockdown of these three HDACs synergistically increased the Kr-h1 promoter activity and its expression, mimicking JH action in inducing Kr-h1. Nevertheless, each HDAC regulates the transcription of different sets of genes, except for a few common genes involved in JH signaling. Furthermore, the knockdown of these HDACs in Ae. aegypti larvae caused different phenotypes apart from delayed pupation: HDAC1 knockdown caused larval growth retardation, body shrinkage, and eventual death; HDAC4 knockdown led to incomplete head capsule shedding after metamorphosis; and HDAC11 knockdown caused higher pupal mortality. Our data demonstrates functional overlap and distinct functions for HDAC1, HDAC4, and HDAC11 in modulating JH signaling, with each HDAC having a unique role in mosquito development.
控制埃及伊蚊对于管理登革热、寨卡病毒、基孔肯雅热和黄热病等蚊媒传播疾病至关重要。控制蚊子的有效方法之一是阻断它们从幼虫阶段到成虫阶段的发育进程。保幼激素（JH）维持幼虫阶段，并确保从幼虫-蛹-成虫阶段过渡的适当发育时间。我们之前的研究表明，组蛋白脱乙酰酶（HDACs）调节赤拟谷盗中保幼激素信号传导和变态发育。然而，HDACs在埃及伊蚊中调节保幼激素信号传导的作用尚不清楚。为了研究HDACs在保幼激素信号传导中的作用，我们在源自埃及伊蚊的Aag-2细胞中敲低每个HDAC编码基因。敲低HDAC1、HDAC4和HDAC11会增加JH初级反应基因Krüppel同源物1（Kr-h1）的表达，该基因会抑制幼虫-蛹的变态发育。此外，同时敲低这三种HDAC会协同增加Kr-h1启动子活性及其表达，模拟JH诱导Kr-h1的作用。然而，除了少数参与JH信号传导的共同基因外，每个HDAC调节不同基因集的转录。此外，在埃及伊蚊幼虫中敲低这些HDAC会导致除化蛹延迟外的不同表型：敲低HDAC1会导致幼虫生长迟缓、身体萎缩并最终死亡；敲低HDAC4会导致变态后头部表皮不完全脱落；敲低HDAC11会导致更高的蛹死亡率。我们的数据证明了HDAC1、HDAC4和HDAC11在调节JH信号传导方面的功能重叠和不同功能，每个HDAC在蚊子发育中都有独特的作用。
