Wnt/?-Catenin Signaling Defines Organizing Centers that Orchestrate Growth and Differentiation of the Regenerating Zebrafish Caudal Fin
- Authors
- Wehner, D., Cizelsky, W., Vasudevaro, M.D., Özhan, G., Haase, C., Kagermeier-Schenk, B., Röder, A., Dorsky, R.I., Moro, E., Argenton, F., Kühl, M., and Weidinger, G.
- ID
- ZDB-PUB-140404-18
- Date
- 2014
- Source
- Cell Reports 6(3): 467-481 (Journal)
- Registered Authors
- Argenton, Francesco, Dorsky, Richard, Haase, Christa, Kagermeier-Schenk, Birgit, Moro, Enrico, Özhan, Günes, Wehner, Daniel, Weidinger, Gilbert
- Keywords
- none
- MeSH Terms
-
- Organ Specificity
- Regeneration/genetics*
- Animal Fins/cytology
- Animal Fins/growth & development*
- Animal Fins/metabolism*
- Models, Biological
- Fibroblast Growth Factors/metabolism
- Cell Differentiation*/genetics
- Ligands
- Body Patterning/genetics
- Gene Expression Regulation, Developmental
- Zebrafish/genetics*
- Zebrafish/growth & development*
- Bone Morphogenetic Proteins/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Osteogenesis
- Animals, Genetically Modified
- Time Factors
- Cell Proliferation
- Osteoblasts/cytology
- Osteoblasts/metabolism
- Epidermis/metabolism
- Epidermis/pathology
- Hedgehog Proteins/metabolism
- Animals
- Genes, Reporter
- Wnt Signaling Pathway*/genetics
- Tretinoin/metabolism
- PubMed
- 24485658 Full text @ Cell Rep.
Zebrafish regenerate their fins via the formation of a population of progenitor cells, the blastema. Wnt/β-catenin signaling is essential for blastemal cell proliferation and patterning of the overlying epidermis. Yet, we find that β-catenin signaling is neither active in the epidermis nor the majority of the proliferative blastemal cells. Rather, tissue-specific pathway interference indicates that Wnt signaling in the nonproliferative distal blastema is required for cell proliferation in the proximal blastema, and signaling in cells lining the osteoblasts directs osteoblast differentiation. Thus, Wnt signaling regulates epidermal patterning, blastemal cell proliferation, and osteoblast maturation indirectly via secondary signals. Gene expression profiling, chromatin immunoprecipitation, and functional rescue experiments suggest that Wnt/β-catenin signaling acts through Fgf and Bmp signaling to control epidermal patterning, whereas retinoic acid and Hedgehog signals mediate its effects on blastemal cell proliferation. We propose that Wnt signaling orchestrates fin regeneration by defining organizing centers that instruct cellular behaviors of adjacent tissues.