Live Imaging of Axolotl Digit Regeneration Reveals Spatiotemporal Choreography of Diverse Connective Tissue Progenitor Pools

Dev Cell. 2016 Nov 21;39(4):411-423. doi: 10.1016/j.devcel.2016.10.013. Epub 2016 Nov 10.


Connective tissues-skeleton, dermis, pericytes, fascia-are a key cell source for regenerating the patterned skeleton during axolotl appendage regeneration. This complexity has made it difficult to identify the cells that regenerate skeletal tissue. Inability to identify these cells has impeded a mechanistic understanding of blastema formation. By tracing cells during digit tip regeneration using brainbow transgenic axolotls, we show that cells from each connective tissue compartment have distinct spatial and temporal profiles of proliferation, migration, and differentiation. Chondrocytes proliferate but do not migrate into the regenerate. In contrast, pericytes proliferate, then migrate into the blastema and give rise solely to pericytes. Periskeletal cells and fibroblasts contribute the bulk of digit blastema cells and acquire diverse fates according to successive waves of migration that choreograph their proximal-distal and tissue contributions. We further show that platelet-derived growth factor signaling is a potent inducer of fibroblast migration, which is required to form the blastema.

Keywords: PDGF signaling; axolotl; blastema formation; brainbow; cell migration; connective tissue; limb regeneration; live imaging; skeletal regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ambystoma mexicanum / physiology*
  • Animals
  • Animals, Genetically Modified
  • Bone and Bones / physiology
  • Cell Movement
  • Cell Proliferation
  • Chondrocytes / cytology
  • Clone Cells
  • Connective Tissue / physiology*
  • Dermis / cytology
  • Extremities / physiology*
  • Fibroblasts / cytology
  • Imaging, Three-Dimensional*
  • Models, Biological
  • Pericytes / cytology
  • Platelet-Derived Growth Factor / metabolism
  • Regeneration / physiology*
  • Signal Transduction
  • Stem Cells / cytology*
  • Time Factors


  • Platelet-Derived Growth Factor