PUBLICATION
Autophagy Regulates Cytoplasmic Remodeling During Cell Reprogramming in a Zebrafish Model of Muscle Regeneration
- Authors
- Saera-Vila, A., Kish, P.E., Louie, K.W., Grzegorski, S.J., Klionsky, D.J., Kahana, A.
- ID
- ZDB-PUB-160729-3
- Date
- 2016
- Source
- Autophagy 12(10): 1864-1875 (Journal)
- Registered Authors
- Grzegorski, Steven, Kahana, Alon, Kish, Phillip
- Keywords
- Atg5, autolysosome, dedifferentiation, electron microscopy, extraocular muscle, regeneration, reprogramming, stem cell, strabismus, zebrafish
- MeSH Terms
-
- Animals
- Apoptosis/genetics
- Autophagy*
- Cellular Reprogramming*
- Cytoplasm/metabolism*
- Energy Metabolism
- Fibroblast Growth Factors/metabolism
- Models, Biological*
- Oculomotor Muscles/physiology*
- Regeneration*
- Up-Regulation
- Zebrafish/genetics
- Zebrafish/physiology*
- PubMed
- 27467399 Full text @ Autophagy
Citation
Saera-Vila, A., Kish, P.E., Louie, K.W., Grzegorski, S.J., Klionsky, D.J., Kahana, A. (2016) Autophagy Regulates Cytoplasmic Remodeling During Cell Reprogramming in a Zebrafish Model of Muscle Regeneration. Autophagy. 12(10):1864-1875.
Abstract
Cell identity involves both selective gene activity and specialization of cytoplasmic architecture and protein machinery. Similarly, reprogramming differentiated cells requires both genetic program alterations and remodeling of the cellular architecture. While changes in genetic and epigenetic programs have been well documented in dedifferentiating cells, the pathways responsible for remodeling the cellular architecture and eliminating specialized protein complexes are not as well understood. Here, we utilize a zebrafish model of adult muscle regeneration to study cytoplasmic remodeling during cell dedifferentiation. We describe activation of autophagy early in the regenerative response to muscle injury, while blocking autophagy using chloroquine or Atg5 and Becn1 knockdown reduced the rate of regeneration with accumulation of sarcomeric and nuclear debris. We further identify Casp3/caspase 3 as a candidate mediator of cellular reprogramming and Fgf signaling as an important activator of autophagy in dedifferentiating myocytes. We conclude that autophagy plays a critical role in cell reprogramming by regulating cytoplasmic remodeling, facilitating the transition to a less differentiated cell identity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping