The aims of this study were i) to characterise differences in the spatial and temporal expression of Pax6 isoforms during murine embryonic development ii) to analyse the expression of Pax6 isoforms in various <i>Pax6 </i>mutant mice during neurogenesis, and iii) to examine the effects of over-expression of the best understood isoforms, in a cell culture system. The overall aim was to elucidate the independent roles of Pax6 isoforms in organogenesis of the central nervous system. RNase protection assay was used to determine the ratio between <i>Pax6 and Pax6+5a </i>transcripts in a number of tissues of the central nervous system during neurogenesis. In most tissues studied, <i>Pax6 </i>is much more prevalent than <i>Pax6+5a </i>at embryonic day 12.5, but the ratio has fallen by embryonic day 18.5. This may be indicative of a change in the role of Pax6, from controlling proliferation to controlling neuronal differentiation. Pax6 protein expression was analysed in mice with 0, 1, 2, 8 and 14 functional copies of <i>Pax6, </i>in order to compare the levels of Pax6 expression between genotypes, and to determine if differential expression of one or more isoforms could be responsible for the mutant phenotypes. Most isoforms are down-regulated in the <i>Pax6<sup>Sey</sup>/+ </i>eye, whilst their relative expression is more varied in the <i>Pax6<sup>Sey</sup>/+ </i>brain. Most isoforms are significantly up-regulated in the brain and eye of mice with 8 or 14 copies of <i>Pax6, </i>but there are no differences between expression levels in the brain of the two genotypes, indicating that Pax6 is subject to autoregulation. Some Pax6 isoforms are observed in the brain of mice thought to lack functional <i>Pax6.</i>
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:660625 |
| Date | January 2005 |
| Creators | Pinson, Jeni |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/29944 |
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