Poster abstracts

Poster number 60 submitted by Mateo Zevallos

Roles of eIF4E homologs in the heart regeneration of zebrafish

Mateo Zevallos (Biomedical Science), Rejenae Dockery ( Biological Chemistry & Pharmacology), Carson McNulty ( Biological Chemistry & Pharmacology), Tessa Zecchino ( Biological Chemistry & Pharmacology), Aaron Goldman ( Biological Chemistry & Pharmacology)

Abstract:
Many limitations to human health are related to the inability to replace damaged tissues. Notably, heart disease is the leading cause of death in humans, because we lack the ability to regenerate lost cardiomyocytes (CMs). Unlike humans, zebrafish have the miraculous ability to fully regenerate their hearts through CM proliferation following any injury to their hearts. A mechanism for activation is unknown, but prior research has found the recapitulation of developmental processes to be related.
Whereas previous studies have heavily characterized transcription, we have chosen to study a family of translation initiation proteins called eIF4E. They function by binding mRNA caps, recruiting them to the ribosome, and initiating translation. Interestingly, whereas land animals contain only one version of the gene, zebrafish have additional homologs. Two are like the canonical version found in humans, while the third, eif4e1c, is only found in aquatic vertebrates.
Due to significant differences in eif4e1c, we hypothesize this unique gene serves a distinct role during heart regeneration and development. Using CRISPR, we deleted all three homologs to differentiate their roles through the mutant effects. We then measured their weight, size, total CM count, and % proliferating cells post-injury through immunohistochemistry.
When comparing homozygous mutant fish to their wildtype siblings we found that deleting eif4e1c caused fish to grow smaller and have fewer actively proliferating cells after injury. Deleting the canonical genes, however, had no effect on size or regeneration. These results suggest that eif4e1c serves a distinct function from the canonical genes during development and regeneration.

Keywords: eIF4E, Translation Initiation, Heart Regeneration