Insulin/IGF signaling and TOR promote vitellogenesis via inducing juvenile hormone biosynthesis

Abstract

28Vitellogenesis, including vitellogenin (Vg) production in the fat body and Vg uptake 29 by maturing oocytes, is of great importance for the successful reproduction of adult 30 females. The endocrinal and nutritional regulation of vitellogenesis differs distinctly in 31 insects. Here, the complex crosstalk between juvenile hormone (JH) and the two 32 nutrient sensors, insulin/IGF signaling (IIS) and target of rapamycin (TOR), was 33 investigated to elucidate the molecular mechanisms regulating vitellogenesis in the 34 American cockroach, Periplaneta americana. Our data showed that a block of JH 35 biosynthesis or JH action arrested vitellogenesis, partially by inhibiting the expression 36 of doublesex (Dsx), a key transcription factor gene involved in the sex determination 37 cascade. Depletion of IIS and TOR blocked both JH biosynthesis and vitellogenesis. 38 Importantly, the JH analog methoprene, but not bovine insulin (to restore IIS) and 39 amino acids (to restore TOR activity), restored vitellogenesis in the neck-ligated (both 40 nutrient-and JH-deficient) cockroaches. Combining classic physiology with modern 41 molecular techniques, we have demonstrated that JH signaling alone is able to induce 42 vitellogenesis and thus ovarian maturation. By contrast, IIS and TOR do not induce 43 vitellogenesis independent of JH, the nutrient sensors promote vitellogenesis in an 44 indirect manner via activating JH biosynthesis. 45 46 KEYWORDS: IIS, TOR, Juvenile hormone, Dsx, vitellogenesis 47 48 Vitellogenesis, an imperative event of insect reproduction, involves vitellogenin (Vg) 49 production in the fat body, the release of Vg into the hemolymph, and Vg uptake by and 50 its modification in maturing oocytes. During the process of Vg uptake, extensive 51 intercellular spaces are formed among follicle cells (follicular patency), allowing the 52 internalization of hemolymph Vg into maturing oocytes by receptor-mediated 53 endocytosis (Raikhel, 2005; Roy et al., 2018). However, the connection between Vg 54 production and the formation of follicular patency has not been determined yet.55