Date of Award

Spring 5-14-2016

Level of Access Assigned by Author

Campus-Only Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

Advisor

Viravuth P. Yin

Second Committee Member

Carol J. Bult

Third Committee Member

Gareth R. Howell

Additional Committee Members

Keith Hutchison

Carol Kim

Abstract

The capacity to regenerate injured appendages and heart tissue is widespread in vertebrates contrary to limited human capacity. We have characterized the molecular pathways that regulate regenerative responses in vertebrates selected to cover a broad taxonomic range. Furthermore, we have identified a core framework of conserved, ancestral gene networks that control progenitor cell activation in these regenerative models. Our systems-level comparative approach has advanced our understanding of the fundamental genetic framework of appendage and heart regeneration in three ways. First, we discovered a conserved microRNA circuit that instructs natural cellular reprogramming during appendage regeneration is shared among three vertebrates that shared a last common ancestor ~420 million years ago. Second, we uncovered a subset differentially expressed long-noncoding RNAs (lncRNAs) at critical stages of heart regeneration that may serve as candidate target genes to augment the limited regenerative capacity of the human heart. Third, we integrated these datasets to advance the development of the Comparative Models of Regeneration Database (RegenDB), a system that enables queries between regeneration competent and deficient systems.

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