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Science 2 November 2007:
Vol. 318. no. 5851, pp. 772 - 777
DOI: 10.1126/science.1147710
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Research Articles

Molecular Basis for the Nerve Dependence of Limb Regeneration in an Adult Vertebrate

Anoop Kumar,1* James W. Godwin,1* Phillip B. Gates,1 A. Acely Garza-Garcia,2 Jeremy P. Brockes1{dagger}

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.

1 Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
2 Division of Molecular Structure, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: j.brockes{at}ucl.ac.uk

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Science. ISSN 0036-8075 (print), 1095-9203 (online)