Affiliations: 1) Baruch College, CUNY, New York, NY; 2) Skirball Institute at NYU School of Medicine, New York, NY; 3) The Whitehead Institute at MIT, Boston, MA
Keywords: n. hormonal control; b. metabolism
Juvenile hormones (JHs) are central coordinators of insect development. These potent small molecules regulate developmental progression between different tissues as well as respond to changes in external conditions. JH titers are dynamic throughout development and the bioavailability of JH is presumed to be tightly controlled by dynamic expression of enzymes responsible for its synthesis and degradation. Two major classes of JH degradation enzymes are Juvenile hormone esterase (Jhe) and Juvenile hormone epoxide hydrolase (Jheh). Due to the importance of JH regulation, insecticides have been designed to block their functions to inhibit the maturation of insect pests and disease vectors.
The endogenous roles of these two distinct classes of JH degradation enzymes in Drosophila are not understood. This knowledge gap may arise from the fact that the D. melanogaster genome encodes two Jhe genes and three Jheh genes. Using CRISPR, we generated Jhe, JheDup null double mutant animals and jheh1,2,3 null mutant animals to understand the functions of these two classes of enzymes. We find that while both jhe,jheDup and jheh1,2,3 larvae exhibit delayed pupariation, the delayed maturation in jheh1,2,3 triple mutant animals is much more dramatic, pupariating three days later than matched wildtype larvae. Interestingly, jhe,jheDup pupae and adults are significantly larger than matched wildtype animals, while jheh1,2,3 animals are smaller. These findings suggest that while all these enzymes can degrade JHs, each class has tissue-specific functions that impact coordinated development and growth. We are currently investigating this exciting postulate, as well as compensatory feedback mechanisms across JH enzymatic classes. Our findings are consistent with global knockdown studies in Bombyx mori1, Leptinotarsa decemlineata2, and Nilaparvata lugens3. Thus, the novel genetic tools we generated in Drosophila will allow us to harness the powerful of this model organism to understand the spatiotemporal and tissue-specific functions of these important enzymes.
References:
1 Zhang, Z., Liu, X., Shiotsuki, T., Wang, Z., Xu, X., Huang, Y., Li, M., Li, K., & Tan, A. (2017). Depletion of juvenile hormone esterase extends larval growth in Bombyx mori. Insect Biochemistry and Molecular Biology, 81, 72–79. https://doi.org/10.1016/j.ibmb.2017.01.001
2 Lu, F.-G., Fu, K.-Y., Guo, W.-C., & Li, G.-Q. (2015). Characterization of two juvenile hormone epoxide hydrolases by RNA interference in the Colorado potato beetle. Gene, 570(2), 264–271. https://doi.org/10.1016/j.gene.2015.06.032
3 Zhao, J., Zhou, Y., Li, X., Cai, W., & Hue, H. (2017). Silencing of juvenile hormone epoxide hydrolase gene (Nljheh) enhances short wing formation in a macropterous strain of the brown planthopper, Nilaparvata lugens. Journal of Insect Physiology, 102, 18–26. https://doi.org/10.1016/j.jinsphys.2017.08.012