Pax6 Is Required for the Differentiation of the Lens Fiber-Cells

Abstract

Purpose: : The developing ocular lens provides an excellent model system 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 from the head surface ectoderm, their later roles during lens-fiber differentiation remain mostly unknown.The aim of this study was to investigate their functions in the process of lens fiber differentiation.

Methods: : Using Cre/loxP mutagenesis, we somatically inactivated Pax6 and Sox2 in a developing lens during differentiation of the secondary lens fibers and explored the regulatory interactions of these two intrinsic factors with the canonical Wnt pathway.

Results: : 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 up-regulated in the Pax6-deficient lenses. However, our study demonstrates that the failed differentiation following loss of Pax6 is independent of β-catenin signaling or Sox2 activity.

Keywords: development