Delaney, Dominic; (2000) Regionalisation of the zebrafish forebrain during early development. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

I have been interested in understanding how the morphologically simple anterior neural plate develops into the complex structures of the adult forebrain. The zebrafish was chosen for this project as it is ideal for looking at the earliest stages of development and a number of genes had already been isolated which were useful for this study. In addition, a large scale mutagenesis using zebrafish has recently been conducted and several of the mutants from these screens were relevant to my project. Through in situ hybridisation studies, I have shown that genes predicted to be involved in early forebrain development are expressed in restricted patterns in the anterior neural plate from the onset of gastrulation. In particular, I have studied the anterior- posterior boundaries present in the prospective neural plate from early gastrulation and the differences between rostral and caudal gene expression patterns. Whilst characterising mutants with disturbed neural plate patterning, I isolated a line of fish which lacks the expression of the anterior neural plate marker anf. anf encodes a homeodomain containing transcription factor and is one of the earliest restricted anterior neural plate markers so far identified. The surprising result was that the absence of cm/'expression did not lead to any obvious developmental defects. To address how patterning genes control later development, I studied their role in the regulation of cell proliferation. To address this, I developed a new technique using an antibody to a phosphorylated histone. I studied the correlation between patterning gene expression and patterns of cell proliferation within the neural plate. During the laboratory's mutagenesis screen looking for early lethal mutants, a novel pigmentation mutant was isolated. I have characterised its pigmentation and other phenotypes.

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