Poster abstracts

Poster number 57 submitted by Mateo Zevallos

The roles of translation initiation factor homologs during zebrafish regeneration

Mateo Zevallos (College of Medicine), Rejenae Dockery (College of Medicine), Carson McNulty (College of Medicine), Tessa Zecchino , Reece Ratermann (College of Medicine), Richard White (College of Medicine)

Abstract:
Heart disease is the leading cause of death due to the human heart’s poor ability to replenish cardiomyocytes (CMs). In contrast, zebrafish use CM proliferation to fully regenerate their hearts by reactivating developmental programs through unknown mechanisms.
While transcriptional regulation is well studied, we examined differences during translation via the initiation factor eIF4E, which binds the 5' mRNA cap, recruiting transcripts to the ribosome. While eIF4E is expressed in all eukaryotes, zebrafish possess a unique family of eIF4E, called eif4e1c, while also containing two paralogs of the canonical variant, eif4ea and eif4eb.
Using CRISPR, we deleted eif4e1c to investigate and found mutant fish had decreased survival, smaller bodies, fewer CMs, and reduced CM proliferation following injury. While intriguing, these results were not confirmation of a specialized eif4e1c function. Thus, we now have explored the canonical eIF4E genes through deletion to differentiate their phenotypes.
Individual and simultaneous deletion of the canonical eif4ea and eif4eb genes both had no impact on survival or size. The ability for fish to develop and survive normally with single and double canonical deletions demonstrates that eif4e1c fully compensates for canonical function. Unexpectedly, single canonical mutants have increased cardiomyocyte proliferation in contrast to eif4e1c mutants. In addition, only canonical mutants and not eif4e1c mutants exhibited impaired fin regeneration. Double mutants though, surprisingly return to baseline regeneration in both tissue types. These results indicate that canonical eIF4E and fish-specific eif4e1c serve distinct translation initiation functions during different forms of regeneration. Additionally, unknown mechanisms regulate the interplay between those pathways such that, when eif4e1c is alone, it functions indistinguishably from wildtype fish during regeneration.

Keywords: Regeneration, Zebrafish, Translation