Williams, Juliet Anne; (1999) Apoptosis in the zebrafish: Mechanisms and consequences. Doctoral thesis (Ph.D), UCL (University College London).

Text Apoptosis_in_the_zebrafish_Me.pdf Download (13MB)

Abstract

During development of the zebrafish apoptosis occurs in a predicable stage specific manner. This programmed cell death (PCD) can be manipulated with staurosporine to induce PCD and the caspase inhibitor, zVADfmk to reduce developmental PCD, staurosporine induced PCD and ectopic PCD in mutants. Rohon Beard cells were studied as a population of neurons which is completely remove by PCD during development. They provide a relatively simple system to determine the mechanisms triggering cell death. Results suggest that death can occur due to a combination of extrinsic factors and intrinsic factors. The hair cells in the neuromasts of the lateral line were found to undergo PCD and dividing support cells produced hair cells to replace them. This death could be inhibited with zVADfmk and induced with hair specific toxins. The rate of division of the support cells changed to match the number of hair cells needed to be replaced. This indicated a feedback system between the hair and support cells. Members of the family of Eph receptors and their ligands were found to be differentially expressed in the hair and support cells although their role is not yet known. A pilot genetic screen was carried out to attempt to elucidate mutants involved in the central cell death machinery, mutants involved with the death of specific populations of cells and mutants on the staurosporine-induced PCD pathway. Although no valuable mutants were found the project illustrated the potential of screens to elucidate novel mutations concerned with PCD. These studies have shown the possibilities of using the zebrafish to answer the many unresolved questions of the role of PCD in development and the mechanisms by which it is orchestrated.

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