昆虫内分泌系统适应不同营养环境而调控个体生长的研究

Insect has evolutionarily become the largest biological population on the earth, partially due to its great success on adapting to starvation and other nutrient-deprivation environments. When the nutrient is rich for an organism, the nutritional signals (mainly via glucose and amino acids) positively regulate all tissues and organs, by activating the PI3K-TORC1 pathway, inhibiting AMPK and FOXO, then inducing cell growth and proliferation, and eventually promoting body growth. When the nutrient is poor or absent, the nutritional signals cease resulting in the arrest of body growth. In insects, the nutritional signals stimulate the endocrine organs to produce and secrete hormones, including insulin-like peptides from the brain insulin producing cells (IPCs), ecdysone (the precursor of the active molting hormone, 20-hydroxyecdysone, 20E) from the prothoracic gland, and an unknown fat body growth factor (FBGF) from the fat body. The nutritional and hormonal signals cross talk with each other, positively or negatively, forming a sophisticated network to adapt to various nutritional environments for regulating body growth. Two model insects, the fruitfly Drosophila melanogaster and the silkworm Bombyx mori, will be used in this project, and their nutritional conditions are artificially manipulated. We aim to solve three major issues which are closely related: (1) to illustrate how the 20E-triggered transcriptional cascade antagonizes the insulin and nutritional signals; (2) to dissect out the signal pathway how the insulin and nutritional signals inhibit the basal level of the 20E signaling; (3) to characterize and identify the FBGF, and to understand the molecular mechanism how FBGF stimulates mitosis in the brain and secretion of insulin-like peptides from the IPCs. The purpose of this project is to understand how the insect endocrine system adapts to various nutritional environments for regulating body growth. The achievements of this project will be important for not only the field of insect science, but also shed lights on endocrinology of animals in general.

昆虫是地球上进化最成功的生物种群，能很好地适应饥荒等特殊营养环境。营养充足时，葡萄糖和氨基酸信号作用于所有组织器官：激活PI3K-TORC1信号、抑制AMPK和FOXO活性，从而诱导细胞生长和分裂、促进个体生长；营养不足则相反。为响应糖和氨基酸信号，昆虫IPCs细胞、前胸腺和脂肪体等内分泌器官分别合成和分泌胰岛素、蜕皮酮和FBGF，三条内分泌信号途径相互促进或制约，以协同适应不同营养环境、共同调控个体生长。本项目拟在原有研究基础上，通过改变果蝇和家蚕的营养环境，1、阐释蜕皮激素抑制胰岛素和营养信号的作用机制；2、剖析胰岛素和营养信号抑制蜕皮激素信号基底水平的信号传导途径；3、鉴定脂肪体分泌的FBGF，揭示FBGF促进脑细胞有丝分裂和IPCs细胞分泌胰岛素的分子机理。本项目旨在借助模式昆虫揭示动物内分泌系统如何协同与互作，在整体水平上适应不同营养环境，从而促进或抑制个体生长的作用机制。

昆虫是地球上进化最成功的生物种群，能很好地适应饥荒等特殊营养环境。营养充足时，葡萄糖和氨基酸信号作用于所有组织器官，营养不足则相反。本项目在原有研究基础上，借助模式昆虫，揭示了动物内分泌系统如何协同与互作，在整体水平上适应不同营养环境，从而促进或抑制个体生长的作用机制。在本项目的资助下，在国际重要SCI刊物发表相关论文15篇。主要取得如下重要结果：（1）证明了20E的受体复合物EcR-USP通过类泛素化来维持正常的20E信号传导；解析了20E初级应答基因E93诱发果蝇变态发育过程中细胞自噬和凋亡的分子机制；在分子水平上阐明了20E初级应答基因E93直接转录调控自噬关键基因ATG1的表达；（2）阐释了20E和JH互作的分子机制及其对昆虫变态发育的调控机理。JH信号通过Kr-h1直接调控前胸腺中ecdysone的合成：在昆虫幼虫时期，类固醇激素20E引起变态发育，从而促进发育的转变，同时类倍半萜烯类激素JH拮抗20E信号，抑制提前变态发育；（3）解析了Ras-Raf-MAPK信号通路通过磷酸化FOXO样转录因子SGF1来促进细胞增殖和存活的分子机制；（4）揭示了20E信号、胰岛素信号以及营养信号对美洲大蠊发育可塑性的影响；（5）筛选了20E拮抗剂，在Kc和Bm12细胞上通过双荧光素酶检测系统从126种化合物中筛选出葫芦素B拮抗活性最强，证实了葫芦素B对20E具有显著拮抗活性。研究结果对益虫利用和害虫防治都具有指导性意义，是昆虫科学的研究前沿，并且对揭示哺乳动物复杂的适应机制也具有重要的借鉴作用。