CAREER: Functional Analysis of microRNAs in Early Development

University Of Delaware, Newark DE

Investigators

Abstract

To understand how a newly fertilized egg becomes a multicellular organism, it is critical to examine how cells within the early embryo integrate various signals to drive development. This research focuses on understanding how cells adopt a specific cell fate as they traverse through the embryo. The cells within the early embryo turn on specific genes, in part, in response to chemical cues they receive from their neighboring cells. This project will discover how genes are controlled by a group of regulatory RNAs. These regulatory RNAs control the level of gene expressions of many genes in several cell types to ensure proper development. Thus, this work contributes to the fundamental understanding of animal development. The project includes education activities that are synergistic to the proposed research project. The first educational activity involves an outreach program at the Delaware Children's Museum where the PI and her students develop a mobile microscope for young children to conduct hands-on, exploratory activities. The second educational activity is to enhance the knowledge base of future early childhood teachers by instilling confidence in science teaching, and by supporting science curriculum development. Inexpensive smartphone microscope platforms are placed in the hands of student teachers to foster future use in their own classrooms. This project is integrated into research training of undergraduate and graduate students and courses taught at the University of Delaware. The proposed educational activities incorporate the PI's expertise in development biology, microscopy, and ongoing research collaborations. MicroRNAs (miRNAs) are highly conserved regulatory RNA molecules that control a myriad of biological processes, including development. In early development, cell specification and pattern formation are controlled by cross-regulation of gene regulatory networks (GRN) and signaling pathways. Signaling morphogen gradients are critical regulators that need to be tightly controlled in order to ensure that the precise organization of the embryo is achieved. This project addresses the overarching hypothesis that miRNAs perform this critical regulatory function. Its goal is to understand how miRNAs integrate GRNs and signaling pathways to drive development. To accomplish this goal, this study uses the sea urchin to study complex developmental processes that are shared by a wide range of organisms. The sea urchin has an exceptionally well-studied GRN and most of its miRNA families consist of a single species, which makes it amenable to unique, powerful functional analysis. To determine the mechanisms by which miRNAs control cell fate specification and directed cell movement during early embryogenesis, the PI will determine regulatory mechanisms of a highly conserved microRNA, miR-31, in the skeletogenic primary mesenchyme cell (PMC) lineage. This project examines how miR-31 coordinately suppresses PMC GRN components and cross-regulates signaling pathways to drive PMC development, using proteomic, transcriptomic, imaging, embryo transplantation, and molecular approaches. Overall, this study will advance the field of miRNA research and contribute to the fundamental understanding of early developmental processes.