Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate |
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Authors: | Kumar Anoop Godwin James W Gates Phillip B Garza-Garcia A Acely Brockes Jeremy P |
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Institution: | Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK. |
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Abstract: | The limb blastemal cells of an adult salamander regenerate the structures distal to the level of amputation, and the surface protein Prod 1 is a critical determinant of their proximodistal identity. The anterior gradient protein family member nAG is a secreted ligand for Prod 1 and a growth factor for cultured newt blastemal cells. nAG is sequentially expressed after amputation in the regenerating nerve and the wound epidermis-the key tissues of the stem cell niche-and its expression in both locations is abrogated by denervation. The local expression of nAG after electroporation is sufficient to rescue a denervated blastema and regenerate the distal structures. Our analysis brings together the positional identity of the blastema and the classical nerve dependence of limb regeneration. |
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