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| Subject Categories: Development |
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| The EMBO Journal
(2006) 25, 5383–5395, doi:10.1038/sj.emboj.7601398 Published online 26 October 2006 |
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| Six3 activation of Pax6 expression is essential for mammalian lens induction and specification |
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| Wei Liu1, Oleg V Lagutin1, Michael Mende2, Andrea Streit2 and Guillermo Oliver1 |
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1 Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN, USA 2 Department of Craniofacial Development, King's College London, London, UK To whom correspondence should be addressed Guillermo Oliver, Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105-2794, USA. Tel.: +1 901 495 2697; Fax: +1 901 526 2907; E-mail: guillermo.oliver@stjude.org Received 31 March 2006; Accepted 26 September 2006; Published online 26 October 2006. |
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| Abstract |
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| The homeobox gene Six3 regulates forebrain development. Here we show that Six3 is also crucial for lens formation. Conditional deletion of mouse Six3 in the presumptive lens ectoderm (PLE) disrupted lens formation. In the most severe cases, lens induction and specification were defective, and the lens placode and lens were absent. In Six3-mutant embryos, Pax6 was downregulated, and Sox2 was absent in the lens preplacodal ectoderm. Using ChIP, electrophoretic mobility shift assay, and luciferase reporter assays, we determined that Six3 activates Pax6 and Sox2 expression. Misexpression of mouse Six3 into chick embryos promoted the ectopic expansion of the ectodermal Pax6 expression domain. Our results position Six3 at the top of the regulatory pathway leading to lens formation. We conclude that Six3 directly activates Pax6 and probably also Sox2 in the PLE and regulates cell autonomously the earliest stages of mammalian lens induction. |
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| Keywords: eye, homeobox, lens, Pax6, Six3 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHSix3 activation of Pax6 expression is essential for mammalian lens induction and specification The EMBO Journal Article Initial Crystallin Synthesis and Lens Fibre Formation are Independent of Lens Morphogenesis Nature Letters to Editor (09 Apr 1971) Nature Letters to Editor (03 Apr 1986) Regulation of αA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin The EMBO Journal Article (17 May 2006) |
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