PUBLICATION

Zebrafish rhabdomyosarcoma reflects the developmental stage of oncogene expression during myogenesis

Authors
Storer, N.Y., White, R.M., Uong, A., Price, E., Nielsen, G.P., Langenau, D.M., and Zon, L.I.
ID
ZDB-PUB-130710-129
Date
2013
Source
Development (Cambridge, England)   140(14): 3040-3050 (Journal)
Registered Authors
Langenau, David, Storer, Narie, Zon, Leonard I.
Keywords
Rhabdomyosarcoma, zebrafish, muscle
Datasets
GEO:GSE39731
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cadherins/genetics
  • Cardiac Myosins/genetics
  • DNA-Binding Proteins/genetics
  • Disease Models, Animal*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Muscle Development*
  • Myosin Light Chains/genetics
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins/genetics
  • Rhabdomyosarcoma/genetics*
  • Stem Cells/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • ras Proteins/genetics
PubMed
23821038 Full text @ Development
Abstract

Rhabdomyosarcoma is a pediatric malignancy thought to arise from the uncontrolled proliferation of myogenic cells. Here, we have generated models of rhabdomyosarcoma in the zebrafish by inducing oncogenic KRASG12D expression at different stages during muscle development. Several zebrafish promoters were used, including the cdh15 and rag2 promoters, which drive gene expression in early muscle progenitors, and the mylz2 promoter, which is expressed in differentiating myoblasts. The tumors that developed differed in their ability to recapitulate normal myogenesis. cdh15:KRASG12D and rag2:KRASG12D fish developed tumors that displayed an inability to complete muscle differentiation as determined by histological appearance and gene expression analyses. By contrast, mylz2:KRASG12D tumors more closely resembled mature skeletal muscle and were most similar to well-differentiated human rhabdomyosarcoma in terms of gene expression. mylz2:KRASG12D fish showed significantly improved survival compared with cdh15:KRASG12D and rag2:KRASG12D fish. Tumor-propagating activity was enriched in myf5-expressing cell populations within all of the tumor types. Our results demonstrate that oncogenic KRASG12D expression at different stages during muscle development has profound effects on the ability of tumor cells to recapitulate normal myogenesis, altering the tumorigenic capability of these cells.

Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping