title: Calcineurin regulates coordinated outgrowth of zebrafish regenerating fins.
abstract: Vertebrates develop organs and appendages in a proportionally coordinated manner, and animals that regenerate them do so to the same dimensions as the original structures. Coordinated proportional growth involves controlled regulation between allometric and isometric growth programs, but it is unclear what executes this control. We show that calcineurin inhibition results in continued allometric outgrowth of regenerating fins beyond their original dimensions. Calcineurin inhibition also maintains allometric growth of juvenile fins and induces it in adult fins. Furthermore, calcineurin activity is low when the regeneration rate is highest, and its activity increases as the rate decreases. Growth measurements and morphometric analysis of proximodistal asymmetry indicate that calcineurin inhibition shifts fin regeneration from a distal growth program to a proximal program. This shift is associated with the promotion of retinoic acid signaling. Thus, we identified a calcineurin-mediated mechanism that operates as a molecular switch between position-associated isometric and allometric growth programs.
authors.affiliation: DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Satu
authors.initials: S
authors.lastname: Kujawski
authors.affiliation: B CUBE, Center for Molecular Bioengineering, Technische Universität Dresden, Arnoldstrasse 18, 01307 Dresden, Germany.
authors.forename: Weilin
authors.initials: W
authors.lastname: Lin
authors.affiliation: DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Kitte
authors.affiliation: DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany; Institute of Biochemistry, Swiss Federal Institute of Technology Zürich, 8093 Zürich, Switzerland.
authors.forename: Mandy
authors.initials: M
authors.lastname: Börmel
authors.affiliation: DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany; Universität Würzburg, 97072 Würzburg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Guruchandar
authors.initials: G
authors.lastname: Arulmozhivarman
authors.affiliation: DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Vogt
authors.affiliation: DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Theil
authors.affiliation: B CUBE, Center for Molecular Bioengineering, Technische Universität Dresden, Arnoldstrasse 18, 01307 Dresden, Germany.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: DFG-Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstrasse 105, 01307 Dresden, Germany. Electronic address: christopher.antos@crt-dresden.de.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Antos
mesh_terms: D058500:Animal Fins / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017403:In Situ Hybridization; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology; D014212:Tretinoin / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D014212:Tretinoin; D019703:Calcineurin; D016559:Tacrolimus