Regulation and function of Hsp70 in zebrafish embryos

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Heat shock proteins (hsps) were originally identified as proteins expressed following exposure of cells to environmental stress such as elevated temperature or toxic metals. Several hsps were subsequently shown to also play important roles as molecular chaperones in normal intracellular protein folding and targeting events, and to be expressed during discrete periods during the development of a number of embryonic tissues. Hsp gene expression is regulated in large part by a small family of transcription factors known as heat shock factors (HSFs). We have shown that the zebrafish hsp70 gene is expressed during a distinct temporal window of normal embryonic lens formation from 28-38 hours post fertilization (hpf) under non-stress conditions, that it is required for normal lens formation, and that lens-specific expression requires the activity of heat shock factor 1 (HSF1). We have also found that the hsp70 gene is strongly upregulated in larval stage zebrafish following exposure to the toxic metal cadmium, and that this stress-induced upregulation occurs in a tissue-specific manner with strong expression in the olfactory neurons and lateral line neuromasts, both important sensory cells in fish. Experiments in this proposal will be aimed at defining the mechanisms by which constitutive lens-specific expression and cadmium-induced olfactory neuron expression of the hsp70 gene are regulated, and the transcription factors involved. Other experiments will further examine the role of the hsp70 gene product in lens formation, particularly in the attenuated apoptotic-like process by which lens fibre organelles are destroyed in order to produce a transparent lens. These experiments will advance our understanding of how expression of a single gene is co-ordinated in a cell-specific manner under different environmental conditions in the context of the intact, developing organism. The end goal of this research program is to generate a comprehensive picture that integrates heat shock gene expression and function into the development and physiology of the developing embryo.