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Publication : Six3 activation of Pax6 expression is essential for mammalian lens induction and specification.

First Author  Liu W Year  2006
Journal  EMBO J Volume  25
Issue  22 Pages  5383-95
PubMed ID  17066077 Mgi Jnum  J:116102
Mgi Id  MGI:3692850 Doi  10.1038/sj.emboj.7601398
Citation  Liu W, et al. (2006) Six3 activation of Pax6 expression is essential for mammalian lens induction and specification. EMBO J 25(22):5383-95
abstractText  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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