Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate

Dev Cell. 2003 Sep;5(3):429-39. doi: 10.1016/s1534-5807(03)00233-8.


The tail of the frog tadpole, comprising spinal cord, muscle, and notochord, regenerates following partial amputation. We show that, in Xenopus, this occurs throughout development, except for a "refractory period" between stages 45 and 47, when tails heal over without regeneration. Regeneration can be enabled during this refractory period by activation of either the BMP or Notch signaling pathways. Conversely, regeneration can be prevented during the later, regenerative, stages by inhibition of either pathway. BMP signaling will cause regeneration of all tissues, whereas Notch signaling activates regeneration of spinal cord and notochord, but not muscle. An activated form of Msx1 can promote regeneration in the same way as BMP signaling. Epistasis experiments suggest that BMP signaling is upstream of Notch signaling but exerts an independent effect on muscle regeneration. The results demonstrate that regenerative capability can be enabled by genetic modifications that reactivate specific components of the developmental program.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amputation / methods
  • Animals
  • Animals, Genetically Modified
  • Bone Morphogenetic Proteins / classification
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Drosophila Proteins / metabolism
  • Enhancer Elements, Genetic / physiology
  • Epistasis, Genetic
  • Gene Expression Regulation, Developmental
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Immunohistochemistry / methods
  • Larva / growth & development
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Muscles / physiology*
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / physiology
  • Receptors, Interleukin / metabolism
  • Receptors, Notch
  • Refractory Period, Electrophysiological / genetics
  • Refractory Period, Electrophysiological / physiology
  • Regeneration / physiology*
  • Signal Transduction / physiology*
  • Spinal Cord / physiology*
  • Tail / growth & development
  • Tail / physiology
  • Time Factors
  • Xenopus / embryology


  • Bone Morphogenetic Proteins
  • Drosophila Proteins
  • HSP70 Heat-Shock Proteins
  • Membrane Proteins
  • Receptors, Interleukin
  • Receptors, Notch
  • dome protein, Drosophila