The Role of Stress Response Factors in the Development and Stress Resistance of the Zebrafish, Danio rerio

Nathan Tucker

Cells respond to physiological and chemical insults by the upregulation and activation of the stress response. This response, also termed the heat shock response, is largely governed by heat shock factors (HSFs), which in turn upregulate the expression of cytoprotective heat shock proteins (HSPs). These HSPs then act to protect the cell against the stress by preventing protein aggregation, altering transcriptional programs, inhibiting pro-apoptotic machinery, or protecting cytoskeletal architecture. However, whereas the overall role of this stress response in protection of tissues and cells against various insults has been reasonable well defined, the roles for specific HSFs and HSPs in this system remain unclear. Furthermore, any additional roles that these proteins may play outside of the canonical stress response pathway have remained largely uninvestigated. This dissertation contains a review of the roles of stress response factors during embryonic development and stress, followed by three studies examining the roles of specific stress response factors in the zebrafish, Danio rerio. The first two studies focus on Hsp27, a member of the small HSP family, in the development and stress resistance of zebrafish tissues. Specifically, the first study details the tissue-specific distribution of Hsp27 in embryos and adults and shows that knockdown of Hsp27 had no overt deleterious effects on development or physiological function of muscular or motor neuron tissues. The second study focuses on the role of Hsp27 in the myocardium of the heat-stressed adult zebrafish. Heat stress drove a profound translocation of Hsp27 to the sarcomere from a cytosolic localization. Utilizing a novel sarcomeric stretch technique, it was determined that Hsp27 bound to the titin filament system of the sarcomeric structure, specifically in the I-band region. The final study evaluated the role of heat shock factor 1 (HSF1) in the protection of brain and eye tissues against ischemia/reperfusion (I/R) injury. Knockdown of HSF1 in developing embryos followed by I/R treatment led to a large increase in apoptosis, but had no effect on HSP levels. These results suggest that HSF1 is a critical member of the response to I/R, but suggests the role may be independent of the canonical stress response pathway.

The Role of Stress Response Factors in the Development and Stress Resistance of the Zebrafish, Danio rerio

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