Regulatory roles of microRNA-1 and microRNA-31 in embryonic development
Date
2022
Authors
Journal Title
Journal ISSN
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Publisher
University of Delaware
Abstract
microRNAs (miRNAs) are highly conserved, small non-coding RNAs that direct post-transcriptional regulation of target messenger RNAs (mRNAs) by binding to the 3’UTR and silencing translation and/or inducing mRNA degradation. miRNAs play important regulatory roles in a myriad of biological processes, including embryogenesis and the physiological functions of cells. While some progress has been made in understanding the function of some miRNAs, relatively little is known about how miRNAs modulate biological pathways and cell cycle progression during embryonic development. Even less is understood on how miRNAs are transcriptionally regulated. ☐ Using Strongylocentrotus purpuratus (purple sea urchin) as our model organism, we take advantage of their small pool of miRNAs, well-characterized gene regulatory networks (GRNs), well-documented early developmental stages, and the conservation of major gene families with humans. The overall research goal is to identify the regulatory functions of miRNAs, incorporate miRNAs into the already well-established sea urchin GRN, and investigate how miRNAs might be transcriptionally regulated during embryogenesis. ☐ Our results indicate that miR-31 and miR-1 play critical regulatory roles in early embryonic development. Both miR-31 and miR-1 regulate skeletogenesis. miR-31 inhibitor injected (or functionally knockdown [KD]) embryos have shortened dorsoventral connecting rods (DVCs), mispatterned skeletogenic primary mesenchyme cells (PMCs), and aberrant Vegf3 expression domain regulated by directly targeting Eve and Wnt1. While miR-1 inhibitor injected embryos have mild defects, miR-1 overexpression (OE) larvae exhibited severe supernumerary branching. Overall, this work demonstrates the fundamental roles of miRNAs in embryogenesis. ☐ Furthermore, we have demonstrated that several miRNAs directly target Dishevelled (Dsh/Dvl), an important component in the highly conserved Wnt signaling pathway that modulates critical aspects in embryonic development. When blocking miRNA suppression of Dvl, we observed increased Dvl protein that is sufficient to result in gut, skeletal, and ciliary embryonic defects. Our preliminary results indicate that Wnt signaling pathways regulate the level of several miRNAs. This led to my overarching hypothesis that miRNAs, signaling pathways, and transcription factors cross-regulate to ensure proper development. ☐ This work demonstrates the regulatory roles of miRNAs in several fundamental developmental processes, including cell migration, pattern formation, morphogenesis, and growth. Overall, integrating post-transcriptional regulation of miRNAs into gene regulatory networks and signaling pathways provide us a better understanding of how various regulatory mechanisms cross-regulate to make a functional embryo.
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Keywords
MicroRNAs, miR-1, miR-31, Sea urchin, Wnt signaling