title: Long-duration muscle dedifferentiation during limb regeneration in axolotls.
abstract: Although still debated, limb regeneration in salamanders is thought to depend on the dedifferentiation of remnant tissue occurring early after amputation and generating the progenitor cells that initiate regeneration. This dedifferentiation has been demonstrated previously by showing the fragmentation of muscle fibers into mononucleated cells and by revealing the contribution of mature muscle fibers to the regenerates by using lineage-tracing studies. Here, we provide additional evidence of dedifferentiation by showing that Pax7 (paired-box protein-7) transcripts are expressed at the ends of remnant muscle fibers in axolotls by using in situ hybridization and by demonstrating the presence of Pax7+ muscle-fiber nuclei in the early bud and mid-bud stages by means of immunohistochemical staining. During the course of regeneration, the remnant muscles did not progress; instead, muscle progenitors migrated out from the remnants and proliferated and differentiated in the new tissues at an early stage of differentiation. The regenerating muscles and remnant muscles were largely disconnected, and this left a gap between them until extremely late in the late stage of differentiation, at which point the new and old muscles connected together. Notably, Pax7 transcripts were detected in the regions of muscles that faced these gaps; thus, Pax7 expression might indicate dedifferentiation in the remnant-muscle ends and partial differentiation in the regenerating muscles. The roles of this long-duration dedifferentiation in the remnants remain unknown. However, the results presented here could support the hypothesis that long-duration muscle dedifferentiation facilitates the connection and fusion between the new and old muscles that are both in an immature state; this is because immature Pax7+ myoblasts readily fuse during developmental myogenesis.
authors: Institute of Biotechnology, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan.
authors: Cheng-Han
authors: CH
authors: Wu
authors: Institute of Biotechnology, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan.
authors: Ting-Yu
authors: TY
authors: Huang
authors: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors: Bo-Sung
authors: BS
authors: Chen
authors: Liver Disease Prevention and Treatment Research Foundation, Taipei, Taiwan.
authors: Ling-Ling
authors: LL
authors: Chiou
authors: Institute of Biotechnology, College of Bioresources and Agriculture, National Taiwan University, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors: Hsuan-Shu
authors: HS
authors: Lee
mesh_terms: D000558:Ambystoma mexicanum / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D054337:Cell Dedifferentiation; D049109:Cell Proliferation; D003001:Cloning, Molecular; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000502:physiology*; D051763:PAX7 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D051763:PAX7 Transcription Factor; D012333:RNA, Messenger