title: A developmentally regulated switch from stem cells to dedifferentiation for limb muscle regeneration in newts.
abstract: The newt, a urodele amphibian, is able to repeatedly regenerate its limbs throughout its lifespan, whereas other amphibians deteriorate or lose their ability to regenerate limbs after metamorphosis. It remains to be determined whether such an exceptional ability of the newt is either attributed to a strategy, which controls regeneration in larvae, or on a novel one invented by the newt after metamorphosis. Here we report that the newt switches the cellular mechanism for limb regeneration from a stem/progenitor-based mechanism (larval mode) to a dedifferentiation-based one (adult mode) as it transits beyond metamorphosis. We demonstrate that larval newts use stem/progenitor cells such as satellite cells for new muscle in a regenerated limb, whereas metamorphosed newts recruit muscle fibre cells in the stump for the same purpose. We conclude that the newt has evolved novel strategies to secure its regenerative ability of the limbs after metamorphosis.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Hibiki Vincent
authors.initials: HV
authors.lastname: Tanaka
authors.affiliation: Faculty of Life Sciences, University of Manchester, Oxford road, Manchester M13 9PT, UK.
authors.forename: Nathaniel Chuen Yin
authors.initials: NCY
authors.lastname: Ng
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Yang Yu
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Martin Miguel
authors.initials: MM
authors.lastname: Casco-Robles
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Maruo
authors.affiliation: Department of Biology, University of Dayton, Dayton, Ohio 45469-2320, USA.
authors.forename: Panagiotis A
authors.initials: PA
authors.lastname: Tsonis
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Chikafumi
authors.initials: C
authors.lastname: Chiba
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation; D019070:Cell Lineage; D058948:Cell Tracking; D005121:Extremities / Q000502:physiology* / Q000637:transplantation; D005260:Female; D007814:Larva / Q000502:physiology; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D008675:Metamorphosis, Biological; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D009132:Muscles / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D012455:Salamandridae / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*; D000097573:Red Fluorescent Protein
chemical_list: D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein