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Date of Award

Fall 12-17-2018

Thesis Access

WSU Access Only Honors Thesis

Degree Name

B.S.

Department

Anatomy and Cell Biology

Faculty Advisor

Ryan Thummel

Abstract

Zebrafish possess the remarkable ability to regenerate multiple tissues and organs. Given that many genetic and cellular components of the zebrafish are conserved in humans, the zebrafish is an ideal model for studying tissue regeneration. This study characterizes the function of midkine-a (mdka) – a heparin binding growth factor known to be strongly upregulated during the regeneration of multiple tissue types – during retinal and fin regeneration in adult zebrafish. Using a mutant mdka knockout line that we generated, we first tested the role of Mdka during retinal regeneration following the intravitreally injection of the neurotoxin Ouabain. Immunohistochemical analysis on mdka mutants and wild-type control animals was used to analyze cellular proliferation following Ouabain-induced damage. Results revealed that mutants had a reduced proliferative response at 3 days post injection (dpi) and increased inflammation. At 28 dpi, mutants displayed significantly diminished regeneration of retinal neurons, suggesting that Mdka is required for proper retinal regeneration. In a separate experiment, we assessed fin regeneration in mdka mutants and wild type control animals following caudal fin amputation. Fin regeneration was characterized by calculating the area outgrowth of newly grown tissue overtime. Immunohistochemical analysis was also utilized to investigate the initial proliferative response. Similar to our findings in retinal regeneration, results revealed an initial reduction in proliferation. However, unlike the retinal tissue, the caudal fin tissue was able to recover to near normal levels overtime. Together, these data suggest that the retina and caudal fin have a different sensitivity to the loss of mdka during regeneration.

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