Defining the regulatory circuit that drives early development of virus-transmitting mosquitoes.

Background: Complex organisms are composed of a wide diversity of cell types, tissues, and organs, yet they all emerged from just a single fertilized cell. Zygotic genome activation is a critical developmental stage in which the early embryonic genome transits from a quiescent state to a transcriptionally active state. The very first steps in this developmental process are similar between different animal species, however, they can differ greatly at the molecular level. Early embryonic development has not been studied in the mosquito Aedes aegypti that is responsible for transmission of important epidemic viruses. Aim: In this project, we will identify the pioneer transcription factors that drive expression of early embryonic genes and are thus essential for zygotic genome activation. Approach: We will establish novel reporters to monitor the ability of transcription factors to drive early embryonic gene expression. These reporters will be used in a targeted approach as well as an untargeted, proteomic approach to identify pioneer transcription factors that drive early development of mosquitoes. Importance: Zygotic genome activation is the most dramatic developmental transition in animals, yet little is known about this important developmental process beyond few genetic model organisms. This project will for the first time identify regulatory factors of early embryonic in mosquitoes. As such, the proposed project will have a major impact on our understanding of early development in animals. Moreover, mosquitoes like Aedes aegypti transmit devastating diseases like dengue hemorrhagic fever and congenital Zika syndrome. Unravelling key steps of embryonic development could be the foundation for novel, innovative mosquito control strategies to reduce the enormous burden of mosquito-transmitted viruses.