Molecular basis for the nerve dependence of limb regeneration in an adult vertebrate

Science. 2007 Nov 2;318(5851):772-7. doi: 10.1126/science.1147710.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD59 Antigens / physiology*
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • Denervation
  • Extremities / innervation
  • Glycosylphosphatidylinositols / physiology
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins / isolation & purification
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Ligands
  • Mice
  • Notophthalmus viridescens
  • Peripheral Nerves / physiology*
  • Regeneration / physiology*
  • Stem Cells / cytology*
  • Two-Hybrid System Techniques

Substances

  • CD59 Antigens
  • Glycosylphosphatidylinositols
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Ligands