饥饿激活JAK/STAT信号促进蜕皮激素合成的生理功能与分子机制

Insects feeding activates IIS/TORC1 signaling, which promotes cell growth and ecdysone biosynthesis in the prothoracic glands (PG) to regulate molting and metamorphosis. Before reaching critical weight in Drosophila, starvation stress inactivates IIS/TORC1 signaling, arrests PG cell growth, decreases ecdysone biosynthesis, results in lethality prior to pupation. After reaching critical weight, even if starvation stress also inactivates IIS/TORC1 signaling and arrests PG cell growth, ecdysone is still sufficient to induce metamorphosis. Preliminary antibody screening showed that starvation activated JAK/STAT signaling and upregulated the ligand Upd3 in Drosophila PG, suggesting that this classical stress signaling is associated with how insect larvae successfully escape starvation stress and become pupae after reaching critical weight. We will extend this study using genetic and molecular tools. (1) We will examine whether starvation stress activates JAK/STAT signaling to promote cell growth and ecdysone synthesis in the PG. (2) We will explore whether the starvation-activated JAK/STAT signaling is dependent on the inactivation of IIS/TOR signaling. (3) We will reveal the universality of JAK/STAT signaling against starvation stress in insects. This study not only brings forward a new insight into how insect hormones are involved in escaping starvation stress, but also provides a theoretical basis for pest control before reaching critical weight.

昆虫取食激活IIS/TORC1信号，促进前胸腺(PG)细胞生长和蜕皮激素(Ecd)合成以调控蜕皮变态。临界体重前饥饿造成果蝇IIS/TORC1信号消失，PG细胞停止生长，Ecd合成降低，化蛹失败而死亡；临界体重后饥饿也造成IIS/TORC1信号降低和PG细胞生长减缓，但合成的Ecd足可导致化蛹。 申请人前期在果蝇中筛选发现，饥饿激活PG中JAK/STAT信号并诱导其配体Upd3高表达，暗示这一经典抗压信号与昆虫在临界体重后逃逸饥饿压力且成功化蛹相关。拟在原有研究基础上，结合遗传与分子手段，（1）明确饥饿是否激活JAK/STAT信号而促进PG细胞生长和Ecd合成；（2）探究饥饿激活的JAK/STAT信号是否因IIS/TORC1信号降低；（3）揭示JAK/STAT信号抗饥饿压力功能是否在昆虫广泛存在。该研究既提出了昆虫逃逸饥饿压力的激素调控新观点，也为“杀虫得趁小”的害虫防治策略提供了理论支持

昆虫取食激活IIS/TORC1信号，促进前胸腺(PG)细胞生长和蜕皮激素(Ecd)合成以调控蜕皮变态。幼虫发育末期，蜕皮激素急速上调，在周边组织中拮抗IIS/TORC1信号，从而中止细胞生长，促进幼虫进入蛹期。本项目旨在研究变态发育过程中，营养信号IIS/TORC1或其他重要因子与蜕皮激素信号之间相互作用的分子机理；同时，探究在营养压力下营养信号缺失对蜕皮激素信号或其他激素信号的调控作用；以及变态发育关键激素蜕皮激素和保幼激素在变态发育或生殖中的新功能。利用转录组学、分子生物学以及遗传学手段，我们获得一系列研究成果：（1）蜕皮激素信号通过AMPK-PP2A通路拮抗营养信号来促进幼虫至蛹的转变；（2）前胸腺分泌JAK配体upd3调控周围组织咽侧体和心侧体中JAK信号通路活力，从而调控变态发育进程；（3）蜕皮激素信号靶标miRNA let-7在脂肪体中通过抑制cdc7来中止细胞生长；（4）保幼激素信号在卵子生成可调控生殖干细胞保持。这些研究成果帮助我们理解昆虫变态发育的激素和营养调控机制，深化变态发育领域相关基础研究，为益虫开发和害虫防治提供理论依据。