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About the Authors:
Chia-Hao Chang
Roles Conceptualization, Investigation
Affiliation: Department of Parasitology, National Taiwan University, Taipei, Taiwan
Yu-Ting Liu
Roles Data curation, Methodology
Affiliation: Department of Parasitology, National Taiwan University, Taipei, Taiwan
Shih-Che Weng
Roles Data curation, Methodology
Affiliation: Department of Parasitology, National Taiwan University, Taipei, Taiwan
I-Yi Chen
Roles Data curation, Methodology
Affiliation: Department of Parasitology, National Taiwan University, Taipei, Taiwan
Po-Nien Tsao
Roles Conceptualization, Resources
Affiliations Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, Research Center for Developmental Biology & Regeneration Medicine, National Taiwan University, Taipei, Taiwan
Shin-Hong Shiao
Roles Conceptualization, Data curation, Writing - original draft, Writing - review & editing
* E-mail: [email protected]
Affiliation: Department of Parasitology, National Taiwan University, Taipei, Taiwan
ORCID http://orcid.org/0000-0002-7749-7807Abstract
The Notch signaling pathway is a highly evolutionarily-conserved cell-cell signaling pathway that regulates many events during development. It plays a pivotal role in the regulation of fundamental cellular processes, such as cell proliferation, stem cell maintenance, and differentiation during embryonic and adult development. However, functions of Notch signaling in Aedes aegypti, the major mosquito vector for dengue, are largely unknown. In this study, we identified a unique feature of A. aegypti Notch (AaNotch) in the control of the sterile-like phenotype in female mosquitoes. Silencing AaNotch with a reverse genetic approach significantly reduced the fecundity and fertility of the mosquito. Silencing AaNotch also resulted in the prevention of micropyle formation, which led to impaired fertilization. In addition, JNK phosphorylation (a signaling molecule in the non-canonical Notch signaling pathway) was inhibited in the absence of AaNotch. Furthermore, treatment with a JNK inhibitor in the mosquito resulted in impaired fecundity and fertility. Taken together, our results demonstrate that non-canonical Notch signaling is essential for controlling fertility in the A. aegypti mosquito.
Author summary
Mosquitoes transmit many devastating diseases, including malaria, dengue, and Zika, which together are responsible for over one million deaths per year. Major reasons for this tragic situation are the unavailability of effective vaccines and drugs for most mosquito-borne diseases, increased resistance of vectors to insecticides, and resistance of pathogens to currently available drugs. A thorough understanding of the molecular machinery involved in mosquito fertility is essential for developing vector control strategies. In this study, we observed a unique feature of the Aedes aegypti Notch (AaNotch) in...