title: FGF and BMP derived from dorsal root ganglia regulate blastema induction in limb regeneration in Ambystoma mexicanum.
abstract: Urodele amphibians have a remarkable organ regeneration ability that is regulated by neural inputs. The identification of these neural inputs has been a challenge. Recently, Fibroblast growth factor (Fgf) and Bone morphogenic protein (Bmp) were shown to substitute for nerve functions in limb and tail regeneration in urodele amphibians. However, direct evidence of Fgf and Bmp being secreted from nerve endings and regulating regeneration has not yet been shown. Thus, it remained uncertain whether they were the nerve factors responsible for successful limb regeneration. To gather experimental evidence, the technical difficulties involved in the usage of axolotls had to be overcome. We achieved this by modifying the electroporation method. When Fgf8-AcGFP or Bmp7-AcGFP was electroporated into the axolotl dorsal root ganglia (DRG), GFP signals were detectable in the regenerating limb region. This suggested that Fgf8 and Bmp7 synthesized in neural cells in the DRG were delivered to the limbs through the long axons. Further knockdown experiments with double-stranded RNA interference resulted in impaired limb regeneration ability. These results strongly suggest that Fgf and Bmp are the major neural inputs that control the organ regeneration ability.
authors.affiliation: Okayama University, Research Core for Interdisciplinary Sciences (RCIS), 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan. Electronic address: satoha@cc.okayama-u.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Satoh
authors.affiliation: Okayama University, Research Core for Interdisciplinary Sciences (RCIS), 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Makanae
authors.affiliation: Okayama University, Research Core for Interdisciplinary Sciences (RCIS), 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Yurie
authors.initials: Y
authors.lastname: Nishimoto
authors.affiliation: Okayama University, Research Core for Interdisciplinary Sciences (RCIS), 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Mitogawa
mesh_terms: D000558:Ambystoma mexicanum / Q000502:physiology*; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005121:Extremities / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000254:growth & development; D049452:Green Fluorescent Proteins / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D009417:Nerve Tissue / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012038:Regeneration / Q000502:physiology*; D013623:Tail
chemical_list: D055419:Bone Morphogenetic Protein 7; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D005346:Fibroblast Growth Factors
keywords: Accessory limb model; BMP; Blastema induction; FGF; Limb regeneration; Nerve factor