PUBLICATION
Distinct Wnt signaling pathways have opposing roles in appendage regeneration
- Authors
- Stoick-Cooper, C.L., Weidinger, G., Riehle, K.J., Hubbert, C., Major, M.B., Fausto N., and Moon, R.T.
- ID
- ZDB-PUB-061229-24
- Date
- 2007
- Source
- Development (Cambridge, England) 134(3): 479-489 (Journal)
- Registered Authors
- Moon, Randall T., Weidinger, Gilbert
- Keywords
- Wnt, zebrafish, regeneration, β-catenin, dickkopf, wnt8, wnt5, pipetail, axin1, masterblind
- MeSH Terms
-
- Adult Stem Cells/cytology
- Adult Stem Cells/physiology
- Animals
- Animals, Genetically Modified
- Base Sequence
- DNA Primers/genetics
- Feedback
- Regeneration/genetics
- Regeneration/physiology*
- Signal Transduction
- Tail
- Wnt Proteins/genetics
- Wnt Proteins/physiology*
- Zebrafish/genetics
- Zebrafish/physiology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- beta Catenin/genetics
- beta Catenin/physiology
- PubMed
- 17185322 Full text @ Development
Citation
Stoick-Cooper, C.L., Weidinger, G., Riehle, K.J., Hubbert, C., Major, M.B., Fausto N., and Moon, R.T. (2007) Distinct Wnt signaling pathways have opposing roles in appendage regeneration. Development (Cambridge, England). 134(3):479-489.
Abstract
In contrast to mammals, lower vertebrates have a remarkable capacity to regenerate complex structures damaged by injury or disease. This process, termed epimorphic regeneration, involves progenitor cells created through the reprogramming of differentiated cells or through the activation of resident stem cells. Wnt/beta-catenin signaling regulates progenitor cell fate and proliferation during embryonic development and stem cell function in adults, but its functional involvement in epimorphic regeneration has not been addressed. Using transgenic fish lines, we show that Wnt/beta-catenin signaling is activated in the regenerating zebrafish tail fin and is required for formation and subsequent proliferation of the progenitor cells of the blastema. Wnt/beta-catenin signaling appears to act upstream of FGF signaling, which has recently been found to be essential for fin regeneration. Intriguingly, increased Wnt/beta-catenin signaling is sufficient to augment regeneration, as tail fins regenerate faster in fish heterozygous for a loss-of-function mutation in axin1, a negative regulator of the pathway. Likewise, activation of Wnt/beta-catenin signaling by overexpression of wnt8 increases proliferation of progenitor cells in the regenerating fin. By contrast, overexpression of wnt5b (pipetail) reduces expression of Wnt/beta-catenin target genes, impairs proliferation of progenitors and inhibits fin regeneration. Importantly, fin regeneration is accelerated in wnt5b mutant fish. These data suggest that Wnt/beta-catenin signaling promotes regeneration, whereas a distinct pathway activated by wnt5b acts in a negative-feedback loop to limit regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping