PUBLICATION
Fgf regulates dedifferentiation during skeletal muscle regeneration in adult zebrafish
- Authors
- Saera-Vila, A., Kish, P.E., Kahana, A.
- ID
- ZDB-PUB-160610-21
- Date
- 2016
- Source
- Cellular Signalling 28(9): 1196-204 (Journal)
- Registered Authors
- Kahana, Alon, Kish, Phillip
- Keywords
- Cell cycle, Cell reprogramming, Heat-shock, MMT, Strabismus
- MeSH Terms
-
- Aging/physiology*
- Animals
- Cell Dedifferentiation*
- Cell Proliferation
- Fibroblast Growth Factors/metabolism*
- Green Fluorescent Proteins/metabolism
- MAP Kinase Signaling System
- Models, Biological
- Muscle, Skeletal/physiology*
- Oculomotor Muscles
- Receptor, Fibroblast Growth Factor, Type 1/metabolism
- Regeneration*
- Zebrafish/physiology*
- PubMed
- 27267062 Full text @ Cell. Signal.
Citation
Saera-Vila, A., Kish, P.E., Kahana, A. (2016) Fgf regulates dedifferentiation during skeletal muscle regeneration in adult zebrafish. Cellular Signalling. 28(9):1196-204.
Abstract
Fibroblast growth factors (Fgfs) regulate critical biological processes such as embryonic development, tissue homeostais, wound healing, and tissue regeneration. In zebrafish, Fgf signaling plays an important role in the regeneration of the spinal cord, liver, heart, fin, and photoreceptors, although its exact mechanism of action is not fully understood. Utilizing an adult zebrafish extraocular muscle (EOM) regeneration model, we demonstrate that blocking Fgf receptor function using either a chemical inhibitor (SU5402) or a dominant-negative transgenic construct (dnFGFR1a:EGFP) impairs muscle regeneration. Adult zebrafish EOMs regenerate through a myocyte dedifferentiation process, which involves a muscle-to-mesenchyme transition and cell cycle reentry by differentiated myocytes. Blocking Fgf signaling reduced cell proliferation and active caspase 3 levels in the regenerating muscle with no detectable levels of apoptosis, supporting the hypothesis that Fgf signaling is involved in the early steps of dedifferentiation. Fgf signaling in regenerating myocytes involves the Mapk/Erk pathway: inhibition of Mek activity with U0126 mimicked the phenotype of the Fgf receptor inhibition on both muscle regeneration and cell proliferation, and activated ERK (p-ERK) was detected in injured muscles by immunofluorescence and western blot. Interestingly, following injury, ERK2 expression is specifically induced and activated by phosphorylation, suggesting a key role in muscle regeneration. We conclude that the critical early steps of myocyte dedifferentiation in EOM regeneration are dependent on Fgf signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping