PUBLICATION
Retinoic acid signaling controls the formation, proliferation and survival of the blastema during adult zebrafish fin regeneration
- Authors
- Blum, N., and Begemann, G.
- ID
- ZDB-PUB-111122-32
- Date
- 2012
- Source
- Development (Cambridge, England) 139(1): 107-16 (Journal)
- Registered Authors
- Begemann, Gerrit
- Keywords
- none
- MeSH Terms
-
- Signal Transduction/genetics*
- Signal Transduction/physiology
- Cell Differentiation/physiology
- Cell Survival/physiology
- In Situ Hybridization
- Cell Proliferation
- In Situ Nick-End Labeling
- Fibroblast Growth Factors/metabolism
- Real-Time Polymerase Chain Reaction
- Zebrafish/physiology*
- Gene Expression Regulation, Developmental/genetics
- Gene Expression Regulation, Developmental/physiology*
- Extremities/physiology*
- Bromodeoxyuridine
- Tretinoin/metabolism*
- Stem Cells/cytology*
- Regeneration/physiology*
- Animals
- beta Catenin
- Wnt Proteins/metabolism
- bcl-Associated Death Protein/metabolism
- PubMed
- 22096078 Full text @ Development
Citation
Blum, N., and Begemann, G. (2012) Retinoic acid signaling controls the formation, proliferation and survival of the blastema during adult zebrafish fin regeneration. Development (Cambridge, England). 139(1):107-16.
Abstract
Adult teleosts rebuild amputated fins through a proliferation-dependent process called epimorphic regeneration, in which a blastema of cycling progenitor cells replaces the lost fin tissue. The genetic networks that control formation of blastema cells from formerly quiescent stump tissue and subsequent blastema function are still poorly understood. Here, we investigated the cellular and molecular consequences of genetically interfering with retinoic acid (RA) signaling for the formation of the zebrafish blastema. We show that RA signaling is upregulated within the first few hours after fin amputation in the stump mesenchyme, where it controls Fgf, Wnt/β-catenin and Igf signaling. Genetic inhibition of the RA pathway at this stage blocks blastema formation by inhibiting cell cycle entry of stump cells and impairs the formation of the basal epidermal layer, a signaling center in the wound epidermis. In the established blastema, RA signaling remains active to ensure the survival of the highly proliferative blastemal population by controlling expression of the anti-apoptotic factor bcl2. In addition, RA signaling maintains blastema proliferation through the activation of growth-stimulatory signals mediated by Fgf and Wnt/β-catenin signaling, as well as by reducing signaling through the growth-inhibitory non-canonical Wnt pathway. The endogenous roles of RA in adult vertebrate appendage regeneration are uncovered here for the first time. They provide a mechanistic framework to understand previous observations in salamanders that link endogenous sources of RA to the regeneration process itself and support the hypothesis that the RA signaling pathway is an essential component of vertebrate tissue regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping