Wnt/beta-Catenin Signalling Pathway Controls Reprogramming: The Basis Of Regeneration In Higher Vertebrates

Objective

Differentiation from zygotes in all cells of the body has been considered a unidirectional route. Recently, however, it has become clear that the inverse path is possible, as the reprogramming of somatic nuclei, i.e. the de-differentiation of somatic cells in pluripotent stem-like cells. To date, reprogramming has been induced in vitro by transferring somatic nuclei into enucleated oocytes, by fusing embryonic stem (ES) cells with somatic cells, and by transferring specific ES-factors into different types of somatic cell. Whether reprogramming can occur in vivo in higher vertebrates and what are the molecular mechanisms and genes driving reprogramming remain unknown. We have recently shown that the activation of Wnt/beta-catenin signalling pathway enhances reprogramming of somatic cells after their fusion with ES cells. Furthermore, our preliminary observations show that Wnt/beta-catenin signalling enhances the reprogramming of spontaneously fused cells. On the other hand, activation of Wnt/beta-catenin signalling pathway controls regeneration in response to damage in Zebra fish tail fin, in Xenopus limbs, and even in adult mammalian tissues, such as hair follicles and retina. Cell fusion is one possible mechanism of regeneration, and our hypothesis is that Wnt/beta-catenin signalling activation triggers the reprogramming in vivo of spontaneously fused hybrids formed between adult stem cells and somatic cells, to regenerate damaged organs. Thus, the specific goals of this project are to identify the beta-catenin target genes, i.e. the reprogrammers that control somatic cell reprogramming, to dissect the molecular mechanisms of reprogramming and to determine if Wnt/beta-catenin-dependent reprogramming of fused cells is the mechanism of regeneration in higher eukaryotes

Fields of science (EuroSciVoc)

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• medical and health sciences clinical medicine ophthalmology
• medical and health sciences medical biotechnology cells technologies stem cells

Keywords

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• somatic cell reprogramming

Programme(s)

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• FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

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• ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology

Call for proposal

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ERC-2009-StG
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Funding Scheme

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ERC-SG - ERC Starting Grant

Host institution

Beneficiaries (2)