The transforming growth factor beta (TGF-β) superfamily and within it, the activin receptor signaling pathway, is a key regulator of many biological processes in vertebrates. Its role in skeletal muscle growth is profound and yet it is not yet fully understood. Some members of this pathway, such as myostatin, have been well characterized as individual units. However, the interactions between activin receptor signaling pathway members, such as Activin A, remain uncharacterized in both mammals and fish. Additionally, the activin receptor signaling pathway in salmonids has been made more complex by two whole genome duplication (WDG) events (Ts3R and Ss4R) resulting in two to four ohnologues of most the genes in this pathway. To study the interactions in the activin receptor signaling pathway in the presence of these ohnologues, we utilized NanoString technology to quantify the expression of fifty-one genes across twenty-three adult tissues in rainbow trout (RBT). From this data, we were able to characterize potential signaling relationships for each tissue as well as to identify the ligands that are produced within skeletal muscle. We were also able to identify divergence of gene function and silencing among some ohnologues. To determine the functional role of activin A in vivo, we utilized NanoString technology to quantify the expression of activin A and related genes across eight developmental timepoints. From this, we identified differential gene expression pre-hatch and post-hatch that allude to similar functions in RBT as seen in mammals. Additionally, we generated gene-edited lines of RBT null for ohnologs of activin A, activin C, and bambi to complete full functional physiology studies. While this research is ongoing, prelimanry expression data from knockout reveals significant changes in related gene expression. This study provides the first complete picture of the expression dynamics of the Activin receptor signaling pathway and thus is a significant initial step toward both understanding WDG duplication event’s important role in evolution and understanding the role functional of activin A function in vivo allowing us to use the pathway for biomedical and agricultural applications.
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Title
INVESTIGATING THE ACTIVIN RECEPTOR PATHWAY AS A KEY REGULATOR OF MUSCLE GROWTH IN RAINBOW TROUT FOLLOWING WHOLE GENOME DUPLICATION EVENTS.
Creators
Jasmine Richman
Contributors
Michael Phelps (Advisor)
Holly Neibergs (Committee Member)
Gordon Murdoch (Committee Member)
Awarding Institution
Washington State University
Academic Unit
Agricultural, Human, and Natural Resource Sciences, College of
Theses and Dissertations
Master of Science (MS), Washington State University