Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate.
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.
Kumar
Anoop
A
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.
Godwin
James W
JW
Gates
Phillip B
PB
Garza-Garcia
A Acely
AA
Brockes
Jeremy P
JP
D000818:Animals; D018957:CD59 Antigens / Q000502:physiology*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003714:Denervation; D005121:Extremities / Q000294:innervation; D017261:Glycosylphosphatidylinositols / Q000502:physiology; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D008024:Ligands; D051379:Mice; D009673:Notophthalmus viridescens; D010525:Peripheral Nerves / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*; D020798:Two-Hybrid System Techniques
D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands