Transdifferentiation from cornea to lens in Xenopus laevis depends on BMP signalling and involves upregulation of Wnt signalling

BMC Dev Biol. 2011 Sep 6:11:54. doi: 10.1186/1471-213X-11-54.

Abstract

Background: Surgical removal of the lens from larval Xenopus laevis results in a rapid transdifferention of central corneal cells to form a new lens. The trigger for this process is understood to be an induction event arising from the unprecedented exposure of the cornea to the vitreous humour that occurs following lens removal. The molecular identity of this trigger is unknown.

Results: Here, we have used a functional transgenic approach to show that BMP signalling is required for lens regeneration and a microarray approach to identify genes that are upregulated specifically during this process. Analysis of the array data strongly implicates Wnt signalling and the Pitx family of transcription factors in the process of cornea to lens transdifferentiation. Our analysis also captured several genes associated with congenital cataract in humans. Pluripotency genes, in contrast, were not upregulated, supporting the idea that corneal cells transdifferentiate without returning to a stem cell state. Several genes from the array were expressed in the forming lens during embryogenesis. One of these, Nipsnap1, is a known direct target of BMP signalling.

Conclusions: Our results strongly implicate the developmental Wnt and BMP signalling pathways in the process of cornea to lens transdifferentiation (CLT) in Xenopus, and suggest direct transdifferentiation between these two anterior eye tissues.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Differentiation*
  • Cell Transdifferentiation
  • Cornea / cytology
  • Cornea / embryology*
  • Cornea / physiology
  • Crystallins / biosynthesis
  • Lens, Crystalline / cytology
  • Lens, Crystalline / embryology*
  • Lens, Crystalline / physiology
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Wnt
  • Regeneration / genetics
  • Regeneration / physiology*
  • Signal Transduction / genetics
  • Wnt Signaling Pathway / physiology*
  • Xenopus Proteins / metabolism
  • Xenopus laevis / embryology*
  • Xenopus laevis / genetics
  • Xenopus laevis / physiology

Substances

  • Bone Morphogenetic Proteins
  • Crystallins
  • Receptors, Wnt
  • Xenopus Proteins