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

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.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.Urodele amphibians, for example the axolotl, are well known for their incredible ability to regenerate appendages, such as the limb. However, axolotls are unable to regenerate the lens of the eye following its removal (lentectomy). In contrast, the anuran amphibian Xenopus laevis, in which limb regeneration is subject to an ontogenic decline leading up to metamorphosis, is able to regenerate a new lens from the overlying central corneal cells (for review see [1,2]). This process was first described by Freeman in 1963, and involves a transdifferentiation of one cell type (corneal epithelium) to another (lens) [3]. It differs from the better-known Wolffian regeneration in adult newts, where a new lens is formed from cells of the pigmented dorsal iris epithelium and is known as cornea to lens transdifferentiation, or CLT [2].The trigger for CLT in vivo is exposure of the outer corneal cells to an unidentified factor present in the vitreous of the eye, most likely originating from the neu