<I>Pax6</I> is a developmentally important, highly conserved transcription factor. <I>Pax6</I> mutations in mouse, man and <I>Drosophila </I>cause eye abnormalities. <I>Pax6</I> mutations in the mouse cause the small eye phenotype. Several small eye alleles have been identified, including <I>Sey </I>and <I>Sey<SUP>Neu</SUP>. </I>The heterozygous small eye mouse (<I>Sey/</I>+) exhibits micropthalmia and anterior segment abnormalities similar to the human conditions of aniridia and Peter's anomaly. The homozygous small eye mouse (<I>Sey/Sey</I>) exhibits anopthalmia, absence of nasal tissues, severe brain defects and cranio-facial abnormalities and is an early post-natal lethal. It is difficult to determine from the small eye homozygous phenotype alone the developmental potential of cells deficient in <I>Pax6</I> during eye and nasal development as the eyes and nasal tissues are completely absent. Therefore, to investigate roles for <I>Pax6 </I>in eye and nasal development, cells deficient for <I>Pax6</I> were incorporated with wild-type cells within aggregation chimaeras. This strategy attempts to rescue <I>Pax6</I> deficient cells into lens and nasal tissue formation. Production of E12.5 <I>Sey<SUP>Neu</SUP>/Sey </I>↔+/+ aggregation chimaeras showed that <I>Sey<SUP>Neu</SUP>/Sey</I> cells were unable to contribute to the lens and nasal epithelium, thus defining a cell autonomous role for <I>Pax6</I> in these tissues. Severe abnormalities of optic cup development were also observed in <I>Sey<SUP>Neu</SUP>/Sey</I> ↔ +/+ chimaeras. Optic cup phenotypes indicated requirements for <I>Pax6</I> in cell-to-cell interaction in the optic cup due to marked segregation between <I>Sey<SUP>Neu</SUP>/Sey </I>cells and wild-type cells. Also, <I>Sey<SUP>Neu</SUP>/Sey</I> cells were found to be excluded from the retinal pigment epithelium (RPE), which indicated a possible cell autonomous role for <I>Pax6</I> in RPE differentiation. Inability of <I>Sey<SUP>Neu</SUP>/Sey</I> cells to contribute to RPE could be due to a failure of mutant cells to be recruited to this differentiation pathway or incomplete or retarded differentiation of <I>Sey<SUP>Neu</SUP>/Sey </I>cells relative to wild-type cells within the chimaeric eye. These possibilities were explored by analysis of expression of <I>Pax6</I> and an early RPE marker, <I>Trp2, </I>in E12.5 and E14.5 <I>Sey<SUP>Neu</SUP>/Sey</I> ↔+/+ chimaeras. These experiments confirmed a role for <I>Pax6</I> in the development of the RPE and indicated that although <I>Sey<SUP>Neu</SUP>/Sey</I> cells were able to be specified as RPE, they were unable to differentiate at the stages examined.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:660844 |
| Date | January 1997 |
| Creators | Quinn, Jane Catherine |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/21474 |
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