Pax6 is essential for lens fiber cell differentiation

Ohad Shaham, April N. Smith, Michael L. Robinson, Makoto M. Taketo, Richard A. Lang, Ruth Ashery-Padan

Research output: Contribution to journalArticlepeer-review

Abstract

The developing ocular lens provides an excellent model system with which to study the intrinsic and extrinsic cues governing cell differentiation. Although the transcription factors Pax6 and Sox2 have been shown to be essential for lens induction, their later roles during lens fiber differentiation remain largely unknown. Using Cre/loxP mutagenesis, we somatically inactivated Pax6 and Sox2 in the developing mouse lens during differentiation of the secondary lens fibers and explored the regulatory interactions of these two intrinsic factors with the canonical Wnt pathway. Analysis of the Pax6-deficient lenses revealed a requirement for Pax6 in cell cycle exit and differentiation into lens fiber cells. In addition, Pax6 disruption led to apoptosis of lens epithelial cells. We show that Pax6 regulates the Wnt antagonist Sfrp2 in the lens, and that Sox2 expression is upregulated in the Pax6-deficient lenses. However, our study demonstrates that the failure of differentiation following loss of Pax6 is independent of β-catenin signaling or Sox2 activity. This study reveals that Pax6 is pivotal for initiation of the lens fiber differentiation program in the mammalian eye.

Original languageEnglish
Pages (from-to)2567-2578
Number of pages12
JournalDevelopment (Cambridge)
Volume136
Issue number15
DOIs
StatePublished - 1 Aug 2009

Keywords

  • Crystallin
  • Lens
  • Mouse
  • Pax6
  • Sox2
  • Wnt
  • β-catenin

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