Hsp27 is required for proper skeletal muscle development

Ryan Christopher Middleton

The cells that make up an organism are constantly bombarded with internal and environmental stressors that create damage to cellular components. These stressors can include external stressors such as hyperthermia, heavy metals, organic solvents and endotoxins, as well as internal stressors, such as oxidative stress. One of the major response pathways cells possess to overcome the effects of stress is the Classical Heat Stress Response pathway. This canonical pathway includes the activation of a small family of transcription factors, called Heat Shock Factors, which regulate two classes of molecular chaperones, also known as Heat Shock Proteins, which promote cell survival. Large heat shock proteins use the energy of ATP to alter the conformational state of damaged or otherwise unfolded proteins. In contrast, small heat shock proteins appear to function by maintaining unfolding proteins in a folding competent state and can perform this function in the absence of ATP. Many small heat shock proteins are expressed in a tissue-specific manner. In addition, these proteins may be differentially expressed in tissues during normal development or in response to physiological events. The small heat shock protein Hsp27 is one of the most highly expressed small heat shock proteins in muscle tissues of vertebrate animals. Muscle-specific expression begins early in development and persists into adulthood. However, the functional significance of this expression is unclear. For example, although several studies have suggested that Hsp27 is required for muscle cell differentiation or survival, other studies have failed to identify defects in muscle tissues of animals lacking Hsp27 expression through gene deletion or suppression procedures. The purpose of this thesis is to establish the expression dynamics of Hsp27 in a developmentally-relevant model, zebrafish (Danio rerio), and investigate its role in skeletal muscle development. Our studies show that inhibition of Hsp27 protein synthesis results in dramatically reduced muscle fiber size, but not fiber number, and that this reduction in size is independent of fiber type. We conclude that Hsp27 is required for proper skeletal muscle development in zebrafish embryos.

Hsp27 is required for proper skeletal muscle development

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