title: Live Imaging of Axolotl Digit Regeneration Reveals Spatiotemporal Choreography of Diverse Connective Tissue Progenitor Pools.
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.
authors.affiliation: 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.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Currie
authors.affiliation: DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Akane
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Ricardo Moreno
authors.initials: RM
authors.lastname: Traspas
authors.affiliation: DFG Research Center for Regenerative Therapies, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Maritta
authors.initials: M
authors.lastname: Schuez
authors.affiliation: 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.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Chara
authors.affiliation: 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.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Tanaka
mesh_terms: D000558:Ambystoma mexicanum / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D001842:Bone and Bones / Q000502:physiology; D002465:Cell Movement; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology; D002999:Clone Cells; D003238:Connective Tissue / Q000502:physiology*; D020405:Dermis / Q000166:cytology; D005121:Extremities / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology; D021621:Imaging, Three-Dimensional; D008954:Models, Biological; D020286:Pericytes / Q000166:cytology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors
chemical_list: D010982:Platelet-Derived Growth Factor
keywords: PDGF signaling; axolotl; blastema formation; brainbow; cell migration; connective tissue; limb regeneration; live imaging; skeletal regeneration