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

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

Author information

1
DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauserstrasse 108, 01307 Dresden, Germany. Electronic address: josh.currie@crt-dresden.de.
2
DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
3
Center for Information Services and High Performance Computing (ZIH), Technische Universität Dresden, 01062 Dresden, Germany; Systems Biology Group (SysBio), Instituto de Física de Líquidos y Sistemas Biológicos (IFLySIB), CONICET, Universidad Nacional de La Plata (UNLP), B1900BTE La Plata, Buenos Aires, Argentina.
4
DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauserstrasse 108, 01307 Dresden, Germany. Electronic address: elly.tanaka@imp.ac.at.

Abstract

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

PMID:
27840105
PMCID:
PMC5127896
DOI:
10.1016/j.devcel.2016.10.013
[Indexed for MEDLINE]
Free PMC Article

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