Pax6 gene in the development of the eyes, nose and brain

• Main Author: Grindley, Justin C.
• Published: University of Edinburgh 1995
• Subjects: 591.35
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651839

<I>Small eye (Sey)</I> mouse embryos, homozygous for mutations in the <I>Pax6 </I>gene, have no eyes, no nasal cavities and no olfactory bulbs (Hogan <I>et al, </I>1986; Hill <I>et al</I>, 1991). Investigating the basis of this striking phenotype could potentially provide valuable insights into the normal processes involved in the development of the eye, nose and brain. <I>Pax6</I> encodes a transcription factor, with two DNA-binding motifs, a paired domain and a <I>paired-</I>type homeodomain (Walther and Gruss, 1991). The work described in this thesis is an investigation into the potential roles of this regulatory gene during normal development. Information obtained from studying the pattern of <I>Pax6</I> mRNA expression in wild-type embryos, and the developmental defects of <I>Sey/Sey</I> animals, was combined to identify processes that may involve PAX6. PAX6 is essential for the formation of lens placodes from surface ectoderm. In normal development, early <I>Pax-6 </I>mRNA expression in a broad domain of surface ectoderm is downregulated, but expression is specifically maintained in the developing lens placode. Thus, phenotype and expression together suggest a role for PAX6 in lens determination. In surface ectoderm in the eye region, PAX6 function is also required for the maintenance of <I>Pax6</I> transcription. Like the lens, the nasal cavities develop from ectodermal placodes that normally express <I>Pax6 </I>mRNA, fail to form in <I>Sey/Sey</I> mice and show PAX6 dependent <I>Pax6</I> mRNA regulation. Analysis of patterns of programmed cell death and absence of nasal region expression from an <I>Msx1</I> transgene in <I>Sey/Sey </I>embryos, suggest a requirement for PAX6 in the transition from presumptive nasal ectoderm to placode, and that <I>Msx1</I>, or genes regulating it, are possible targets for PAX6.