Forkhead box O (FOXO) functions as the terminal transcription factor of the insulin signaling pathway and regulates multiple physiological processes in many organisms, including lifespan in insects. However, how FOXO interacts with hormone signaling to modulate insect growth and development is largely unknown. Here, using the transgene-based CRISPR/Cas9 system, we generated and characterized mutants of the silkworm Bombyx mori FOXO (BmFOXO) to elucidate its physiological functions during development of this lepidopteran insect. The BmFOXO mutant (FOXO-M) exhibited growth delays from the first larval stage and showed precocious metamorphosis, pupating at the end of the fourth instar (trimolter) rather than at the end of the fifth instar as in the wild-type (WT) animals. However, different from previous reports on precocious metamorphosis caused by juvenile hormone (JH) deficiency in silkworm mutants, the total developmental time of the larval period in the FOXO-M was comparable with that of the WT. Exogenous application of 20-hydroxyecdysone (20E) or of the JH analog rescued the trimolter phenotype. RNA-seq and gene expression analyses indicated that genes involved in JH degradation but not in JH biosynthesis were up-regulated in the FOXO-M compared with the WT animals. Moreover, we identified several FOXO-binding sites in the promoter of genes coding for JH-degradation enzymes. These results suggest that FOXO regulates JH degradation rather than its biosynthesis, which further modulates hormone homeostasis to control growth and development in B. mori. In conclusion, we have uncovered a pivotal role for FOXO in regulating JH signaling to control insect development.

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Published in The Journal of Biological Chemistry, v. 292, no. 28, p. 11659-11669.

This research was originally published in The Journal of Biological Chemistry. Baosheng Zeng, Yuping Huang, Jun Xu, Takahiro Shiotsuki, Hua Bai, Subba Reddy Palli, Yongping Huang, and Anjiang Tan. The FOXO Transcription Factor Controls Insect Growth and Development by Regulating Juvenile Hormone Degradation in the Silkworm, Bombyx mori. J. Biol. Chem. 2017; 292:11659-11669. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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This work was supported by Strategic Priority Research Program of Chinese Academy of Sciences Grant XDB11010600, National Basic Research Program of China Grant 2015CB755703, National Science Foundation of China Grants 31420103918 and 31530072, and Chinese Academy of Sciences Grant KJZD-EW-L12-02.

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This article contains supplemental Tables S1 and S2 and Figs. S1–S9.

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