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

Wei Liu, Oleg V. Lagutin, Michael Mende, Andrea Streit, Guillermo Oliver

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5383-5395
Number of pages13
JournalEMBO Journal
Volume25
Issue number22
DOIs
StatePublished - Nov 15 2006
Externally publishedYes

Keywords

  • Eye
  • Homeobox
  • Lens
  • Pax6
  • Six3

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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