Combinatorial function of ETS transcription factors in the developing vasculature

Pham, V.N., Lawson, N.D., Mugford, J.W., Dye, L., Castranova, D., Lo, B., and Weinstein, B.M.
Developmental Biology   303(2): 772-783 (Journal)
Registered Authors
Castranova, Dan, Lawson, Nathan, Lo, Brigid, Mugford, Joshua, Pham, Van, Weinstein, Brant M.
Zebrafish, ETS transcription factors, Intersegmental vessels, Vascular development, Angiogenesis
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Blood Vessels/embryology*
  • Blood Vessels/metabolism*
  • Chromosome Mapping
  • Cloning, Molecular
  • DNA Primers/genetics
  • Gene Expression Regulation, Developmental
  • Hematopoiesis/genetics
  • Morphogenesis/genetics
  • Mutation
  • Neovascularization, Physiologic/genetics
  • Oligodeoxyribonucleotides, Antisense/genetics
  • Proto-Oncogene Protein c-ets-1/genetics
  • Proto-Oncogene Protein c-ets-1/metabolism
  • Proto-Oncogene Protein c-fli-1/genetics
  • Proto-Oncogene Protein c-fli-1/metabolism
  • Proto-Oncogene Proteins c-ets/genetics
  • Proto-Oncogene Proteins c-ets/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
17125762 Full text @ Dev. Biol.
Members of the ETS family of transcription factors are among the first genes expressed in the developing vasculature, but loss-of-function experiments for individual ETS factors in mice have not uncovered important early functional roles for these genes. However, multiple ETS factors are expressed in spatially and temporally overlapping patterns in the developing vasculature, suggesting possible functional overlap. We have taken a comprehensive approach to exploring the function of these factors during vascular development by employing the genetic and experimental tools available in the zebrafish to analyze four ETS family members expressed together in the zebrafish vasculature; fli1, fli1b, ets1, and etsrp. We isolated and characterized an ENU-induced mutant with defects in trunk angiogenesis and positionally cloned the defective gene from this mutant, etsrp. Using the etsrp morpholinos targeting each of the four genes, we show that the four ETS factors function combinatorially during vascular and hematopoietic development. Reduction of etsrp or any of the other genes alone results in either partial or no defects in endothelial differentiation, while combined reduction in the function of all four genes causes dramatic loss of endothelial cells. Our results demonstrate that combinatorial ETS factor function is essential for early endothelial specification and differentiation.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes