The role of Pax-6 in lens regeneration

Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14848-53. doi: 10.1073/pnas.0601949103. Epub 2006 Sep 26.

Abstract

Pax-6 is a master regulator of eye development and is expressed in the dorsal and ventral iris during newt lens regeneration. We show that expression of Pax-6 during newt lens regeneration coincides with cell proliferation. By knocking down expression of Pax-6 via treatment with morpholinos, we found that proliferation of iris pigment epithelial cells was dramatically reduced both in vitro and in vivo, and, as a result, lens regeneration was significantly retarded. However, induction of dedifferentiation in the dorsal iris was not inhibited. Pax-6 knockdown early in lens regeneration resulted in inhibition of crystallin expression and retardation of lens fiber induction. Once crystallin expression and differentiation of lens fibers has ensued, however, loss of function of Pax-6 did not affect crystallin expression and lens fiber maintenance, even though the effects on proliferation persisted. These results conclusively show that Pax-6 is associated with distinct early events during lens regeneration, namely control of cell proliferation and subsequent lens fiber differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Epithelial Cells / cytology
  • Eye Proteins / metabolism*
  • Homeodomain Proteins / metabolism*
  • Iris / cytology
  • Lens, Crystalline / drug effects
  • Lens, Crystalline / physiology*
  • Oligonucleotides, Antisense / pharmacology
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / deficiency
  • Paired Box Transcription Factors / metabolism*
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / drug effects
  • Regeneration* / drug effects
  • Repressor Proteins / metabolism*
  • Salamandridae

Substances

  • Eye Proteins
  • Homeodomain Proteins
  • Oligonucleotides, Antisense
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Repressor Proteins