title: Repeated removal of developing limb buds permanently reduces appendage size in the highly-regenerative axolotl.
abstract: Matching appendage size to body size is fundamental to animal function. Generating an appropriately-sized appendage is a robust process executed during development which is also critical for regeneration. When challenged, larger animals are programmed to regenerate larger limbs than smaller animals within a single species. Understanding this process has important implications for regenerative medicine. To approach this complex question, models with altered appendage size:body size ratios are required. We hypothesized that repeatedly challenging axolotls to regrow limb buds would affect their developmental program resulting in altered target morphology. We discovered that after 10 months following this experimental procedure, limbs that developed were permanently miniaturized. This altered target morphology was preserved upon amputation and regeneration. Future experiments using this platform should provide critical information about how target limb size is encoded within limb progenitors.
authors.affiliation: Harvard Medical School, the Harvard stem Cell Institute, and the Department of Orthopedic Surgery, Brigham & Women's Hospital, Cambridge, MA 02139, USA.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bryant
authors.affiliation: Harvard Medical School, the Harvard stem Cell Institute, and the Department of Orthopedic Surgery, Brigham & Women's Hospital, Cambridge, MA 02139, USA; Allen Discovery Center at Tufts, Medford, MA 02155, USA.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Sousounis
authors.affiliation: Department of Biology, Northeastern University, Boston, MA 02115, USA.
authors.forename: Johanna E
authors.initials: JE
authors.lastname: Farkas
authors.affiliation: Harvard Medical School, the Harvard stem Cell Institute, and the Department of Orthopedic Surgery, Brigham & Women's Hospital, Cambridge, MA 02139, USA.
authors.forename: Sevara
authors.initials: S
authors.lastname: Bryant
authors.affiliation: Harvard Medical School, the Harvard stem Cell Institute, and the Department of Orthopedic Surgery, Brigham & Women's Hospital, Cambridge, MA 02139, USA.
authors.forename: Neng
authors.initials: N
authors.lastname: Thao
authors.affiliation: Harvard Medical School, the Harvard stem Cell Institute, and the Department of Orthopedic Surgery, Brigham & Women's Hospital, Cambridge, MA 02139, USA.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Guzikowski
authors.affiliation: Department of Biology, Northeastern University, Boston, MA 02115, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Monaghan
authors.affiliation: Allen Discovery Center at Tufts, Medford, MA 02155, USA; Tufts Center for Regenerative and Developmental Biology, Medford, MA 02155, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
authors.affiliation: Harvard Medical School, the Harvard stem Cell Institute, and the Department of Orthopedic Surgery, Brigham & Women's Hospital, Cambridge, MA 02139, USA; Allen Discovery Center at Tufts, Medford, MA 02155, USA. Electronic address: jwhited@bwh.harvard.edu.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Whited
mesh_terms: D000558:Ambystoma mexicanum / Q000196:embryology*; D000671:Amputation, Surgical; D000818:Animals; D004480:Ectromelia / Q000473:pathology; D018878:Limb Buds / Q000002:abnormalities / Q000196:embryology* / Q000294:innervation / Q000473:pathology*; D009417:Nerve Tissue / Q000473:pathology; D009929:Organ Size; D012038:Regeneration
keywords: Axolotl; Development; Growth; Limb; Morphogenesis; Regeneration