Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate.
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.
Beck
Caroline W
CW
Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, BA2 7AY, Bath, United Kingdom.
Christen
Bea
B
Slack
Jonathan M W
JM
D000671:Amputation, Surgical / Q000379:methods; D000818:Animals; D030801:Animals, Genetically Modified; D019485:Bone Morphogenetic Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007814:Larva / Q000254:growth & development; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D018123:Receptors, Interleukin / Q000378:metabolism; D051880:Receptors, Notch; D012032:Refractory Period, Electrophysiological / Q000235:genetics / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*; D013623:Tail / Q000254:growth & development / Q000502:physiology; D013997:Time Factors; D014981:Xenopus / Q000196:embryology
D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D051880:Receptors, Notch; C444499:dome protein, Drosophila