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Title: Defining roles for Pax6 in fetal mouse development : investigations of the developmental potential of cells deficient for Pax6 using small eye homozygous mutants and aggregation chimaeras
Author: Quinn, Jane Catherine
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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Pax6 is a developmentally important, highly conserved transcription factor. Pax6 mutations in mouse, man and Drosophila cause eye abnormalities. Pax6 mutations in the mouse cause the small eye phenotype. Several small eye alleles have been identified, including Sey and SeyNeu. The heterozygous small eye mouse (Sey/+) exhibits micropthalmia and anterior segment abnormalities similar to the human conditions of aniridia and Peter's anomaly. The homozygous small eye mouse (Sey/Sey) 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 Pax6 during eye and nasal development as the eyes and nasal tissues are completely absent. Therefore, to investigate roles for Pax6 in eye and nasal development, cells deficient for Pax6 were incorporated with wild-type cells within aggregation chimaeras. This strategy attempts to rescue Pax6 deficient cells into lens and nasal tissue formation. Production of E12.5 SeyNeu/Sey ↔+/+ aggregation chimaeras showed that SeyNeu/Sey cells were unable to contribute to the lens and nasal epithelium, thus defining a cell autonomous role for Pax6 in these tissues. Severe abnormalities of optic cup development were also observed in SeyNeu/Sey ↔ +/+ chimaeras. Optic cup phenotypes indicated requirements for Pax6 in cell-to-cell interaction in the optic cup due to marked segregation between SeyNeu/Sey cells and wild-type cells. Also, SeyNeu/Sey cells were found to be excluded from the retinal pigment epithelium (RPE), which indicated a possible cell autonomous role for Pax6 in RPE differentiation. Inability of SeyNeu/Sey 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 SeyNeu/Sey cells relative to wild-type cells within the chimaeric eye. These possibilities were explored by analysis of expression of Pax6 and an early RPE marker, Trp2, in E12.5 and E14.5 SeyNeu/Sey ↔+/+ chimaeras. These experiments confirmed a role for Pax6 in the development of the RPE and indicated that although SeyNeu/Sey cells were able to be specified as RPE, they were unable to differentiate at the stages examined.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available