PUBLICATION

Time Point-based Integrative Analyses of Deep-transcriptome Identify Four Signal Pathways in Blastemal Regeneration of Zebrafish Lower Jaw

Authors
Zhang, H., Wang, X., Lv, K., Gao, S., Wang, G., Fan, C., Zhang, X.A., Yan, J.
ID
ZDB-PUB-141126-5
Date
2015
Source
Stem cells (Dayton, Ohio)   33(3): 806-18 (Journal)
Registered Authors
Yan, Jizhou
Keywords
RNA-sequencing, blastemal regeneration, foxi1, tissue engineering, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Bone Regeneration/physiology*
  • Cell Differentiation/genetics
  • Cell Transdifferentiation/genetics
  • Guided Tissue Regeneration
  • Jaw/cytology
  • Jaw/physiology*
  • Signal Transduction/genetics
  • Transcriptome
  • Zebrafish
PubMed
25420467 Full text @ Stem Cells
Abstract
There has been growing interest in applying tissue engineering to stem cell-based regeneration therapies. We have previously reported that zebrafish can faithfully regenerate complicated tissue structures through blastemal cell type conversions and tissue reorganization. To unveil the regenerative factors and engineering arts of blastemal regeneration, we conducted transcriptomal analyses at four time points corresponding to preamputation, reepitheliation, blastemal formation, and respecification. By combining the hierarchical Gene Ontology (GO) term network, the DAVID annotation system, and Euclidean distance clustering, we identified four signaling pathways: foxi1-foxo1b-pou3f1, pax3a-mant3a- col11/col2, pou5f1-cdx4- kdrl, and isl1-wnt11 PCP-sox9a. Results from immunohistochemical staining and promoter-driven transgenic fish suggest that these pathways respectively define wound epidermis reconstitution, cell type conversions, blastemal angiogenesis/vasculogenesis, and cartilage matrix-orientation. Foxi1 morpholino-knockdown caused expansions of Foxo1b- and Pax3a-expression in the basal layer-blastemal junction region. Moreover, foxi1 morphants displayed increased sox9a and hoxa2b transcripts in the embryonic pharyngeal arches. Thus, a Foxi1 signal switch is required to establish correct tissue patterns, including reepitheliation and blastema formation. This study provides novel insight into a blastema regeneration strategy devised by epithelial cell transdifferentiation, blood vessel engineering, and cartilage matrix deposition. This article is protected by copyright. All rights reserved.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping