title: Fundamental differences in dedifferentiation and stem cell recruitment during skeletal muscle regeneration in two salamander species.
abstract: Salamanders regenerate appendages via a progenitor pool called the blastema. The cellular mechanisms underlying regeneration of muscle have been much debated but have remained unclear. Here we applied Cre-loxP genetic fate mapping to skeletal muscle during limb regeneration in two salamander species, Notophthalmus viridescens (newt) and Ambystoma mexicanum (axolotl). Remarkably, we found that myofiber dedifferentiation is an integral part of limb regeneration in the newt, but not in axolotl. In the newt, myofiber fragmentation results in proliferating, PAX7(-) mononuclear cells in the blastema that give rise to the skeletal muscle in the new limb. In contrast, myofibers in axolotl do not generate proliferating cells, and do not contribute to newly regenerated muscle; instead, resident PAX7(+) cells provide the regeneration activity. Our results therefore show significant diversity in limb muscle regeneration mechanisms among salamanders and suggest that multiple strategies may be feasible for inducing regeneration in other species, including mammals.
authors.affiliation: Technische Universität Dresden, DFG Research Center for Regenerative Therapies, CRTD.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Sandoval-Guzmán
authors.affiliation: Department of Cell and Molecular Biology, Centre of Developmental Biology for Regenerative Medicine, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Technische Universität Dresden, DFG Research Center for Regenerative Therapies, CRTD; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Shahryar
authors.initials: S
authors.lastname: Khattak
authors.affiliation: Technische Universität Dresden, DFG Research Center for Regenerative Therapies, CRTD; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Maritta
authors.initials: M
authors.lastname: Schuez
authors.affiliation: Technische Universität Dresden, DFG Research Center for Regenerative Therapies, CRTD.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Roensch
authors.affiliation: Technische Universität Dresden, DFG Research Center for Regenerative Therapies, CRTD.
authors.forename: Eugeniu
authors.initials: E
authors.lastname: Nacu
authors.affiliation: Technische Universität Dresden, DFG Research Center for Regenerative Therapies, CRTD.
authors.forename: Akira
authors.initials: A
authors.lastname: Tazaki
authors.affiliation: Department of Cell and Molecular Biology, Centre of Developmental Biology for Regenerative Medicine, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Alberto
authors.initials: A
authors.lastname: Joven
authors.affiliation: Technische Universität Dresden, DFG Research Center for Regenerative Therapies, CRTD. Electronic address: elly.tanaka@crt-dresden.de.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Tanaka
authors.affiliation: Department of Cell and Molecular Biology, Centre of Developmental Biology for Regenerative Medicine, Karolinska Institute, SE-171 77 Stockholm, Sweden. Electronic address: andras.simon@ki.se.
authors.forename: András
authors.initials: A
authors.lastname: Simon
mesh_terms: D000558:Ambystoma mexicanum / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D054337:Cell Dedifferentiation; D049109:Cell Proliferation; D005121:Extremities / Q000502:physiology; D017930:Genes, Reporter; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D007814:Larva / Q000502:physiology; D008648:Mesoderm / Q000166:cytology / Q000637:transplantation; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology*; D051763:PAX7 Transcription Factor / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D012455:Salamandridae / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*
chemical_list: D051763:PAX7 Transcription Factor