The non-canonical Notch signaling is essential for the control of fertility in Aedes aegypti.

Chia-Hao Chang,Shih-Che Weng,I-Yi Chen,Po-Nien Tsao,Shin-Hong Shiao,Yu-Ting Liu,Lyric C Bartholomay

doi:10.1371/journal.pntd.0006307

Abstract

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.

Highlights

Mosquitoes are highly-effective vectors that transmit many devastating diseases, including malaria, dengue, and Zika
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 mosquitoborne 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

Summary

Introduction

Mosquitoes are highly-effective vectors that transmit many devastating diseases, including malaria, dengue, and Zika. The outbreak of Zika became a threat to global health and poses a significant public health challenge [8, 9] Major reasons for this tragic situation are the unavailability of effective vaccines, an increase of vector resistance to insecticides, and pathogen resistance to drugs [10,11,12]. Inhibition of TOR in fat body culture systems, by either rapamycin or RNA interference (RNAi)-mediated gene depletion, results in a significant down-regulation of Vg gene transcription after amino acid stimulation [15, 16]. Results of these studies suggest that a thorough understanding of the molecular machinery involved in mosquito fertility will be useful for developing vector control strategies

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Discussion

Conclusion