title: ATP oscillations mediate inductive action of FGF and Shh signalling on prechondrogenic condensation.
abstract: Skeletal patterns are prefigured by prechondrogenic condensation. Morphogens such as fibroblast growth factor (FGF) and sonic hedgehog (Shh) specify the skeletal patterns in limb development. However, how morphogens regulate prechondrogenic condensation has remained unclear. Recently, it was demonstrated that synchronized Adenosine triphosphate (ATP) oscillations play a critical role in prechondrogenic condensation. Thus, the present study has focused on whether ATP oscillations mediate the actions of major developmental morphogens such as FGF and Shh on prechondrogenic condensation. It has been shown that both FGF and Shh signalling promoted cellular condensation but not chondrogenic differentiation and also induced ATP oscillations. In addition, blockage of FGF and Shh signalling prevented both ATP oscillations and prechondrogenic condensation. Furthermore, it was found that inhibition of ATP oscillations suppressed FGF/Shh-induced prechondrogenic condensation. These results indicate that ATP oscillations mediate the actions of FGF and Shh signalling on prechondrogenic condensation. This study proposes that morphogens organize skeletal patterns via ATP oscillations.
authors.affiliation: Regenerative Medicine/Tissue Engineering Division, Research Center for Cooperative Projects, Graduate School of Medicine, Hokkaido University, N-15 W-7, Kita-ku, Sapporo, 060-8638, Japan. kwonhj@med.hokudai.ac.jp
authors.forename: Hyuck Joon
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002460:Cell Line / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects*; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology*; D002934:Cinnamates / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017930:Genes, Reporter; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology; D008163:Luminescent Measurements; D051379:Mice; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: C542465:3-keto-N-aminoethylaminoethylcaproyldihydrocinnamoyl cyclopamine; D002934:Cinnamates; D053823:Hedgehog Proteins; D007328:Insulin; D011758:Pyrroles; C105686:SU 5402; C465570:Shh protein, mouse; D014704:Veratrum Alkaloids; D016222:Fibroblast Growth Factor 2; D000255:Adenosine Triphosphate