title: Autophagy is required for zebrafish caudal fin regeneration.
abstract: Regeneration is the ability of multicellular organisms to replace damaged tissues and regrow lost body parts. This process relies on cell fate transformation that involves changes in gene expression as well as in the composition of the cytoplasmic compartment, and exhibits a characteristic age-related decline. Here, we present evidence that genetic and pharmacological inhibition of autophagy - a lysosome-mediated self-degradation process of eukaryotic cells, which has been implicated in extensive cellular remodelling and aging - impairs the regeneration of amputated caudal fins in the zebrafish (Danio rerio). Thus, autophagy is required for injury-induced tissue renewal. We further show that upregulation of autophagy in the regeneration zone occurs downstream of mitogen-activated protein kinase/extracellular signal-regulated kinase signalling to protect cells from undergoing apoptosis and enable cytosolic restructuring underlying terminal cell fate determination. This novel cellular function of the autophagic process in regeneration implies that the role of cellular self-digestion in differentiation and tissue patterning is more fundamental than previously thought.
authors: Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors: M
authors: M
authors: Varga
authors: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary.
authors: M
authors: M
authors: Sass
authors: Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors: D
authors: D
authors: Papp
authors: Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors: K
authors: K
authors: Takács-Vellai
authors: BioTalentum Ltd., H-2100, Gödöllő, Hungary.
authors: J
authors: J
authors: Kobolak
authors: BioTalentum Ltd., H-2100, Gödöllő, Hungary.
authors: A
authors: A
authors: Dinnyés
authors: Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
authors: D J
authors: DJ
authors: Klionsky
authors: Department of Genetics, Eötvös Loránd University, Budapest, Hungary.
authors: T
authors: T
authors: Vellai
mesh_terms: D058500:Animal Fins / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D000071187:Autophagy-Related Protein 5; D002070:Butadienes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction / Q000187:drug effects; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C572697:Atg5 protein, zebrafish; D000071187:Autophagy-Related Protein 5; D002070:Butadienes; D004791:Enzyme Inhibitors; D018942:Macrolides; D009570:Nitriles; D016376:Oligonucleotides, Antisense; C113580:U 0126; D029961:Zebrafish Proteins; C040929:bafilomycin A1; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases