PUBLICATION

ETS Factors Regulate Vegf-Dependent Arterial Specification

Authors
Wythe, J.D., Dang, L.T., Devine, W.P., Boudreau, E., Artap, S.T., He, D., Schachterle, W., Stainier, D.Y., Oettgen, P., Black, B.L., Bruneau, B.G., and Fish, J.E.
ID
ZDB-PUB-130729-1
Date
2013
Source
Developmental Cell   26(1): 45-58 (Journal)
Registered Authors
Dang, Lan, Fish, Jason E., Stainier, Didier, Wythe, Joshua
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified/embryology
  • Animals, Genetically Modified/metabolism
  • Aorta/metabolism
  • Aorta/physiology*
  • Binding Sites
  • Endocardium/embryology
  • Endocardium/metabolism
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism
  • MAP Kinase Signaling System
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Mice
  • Organ Specificity
  • Proto-Oncogene Proteins/genetics
  • Proto-Oncogene Proteins/metabolism
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism
  • Trans-Activators/genetics
  • Trans-Activators/metabolism
  • Transcription, Genetic
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
PubMed
23830865 Full text @ Dev. Cell
Abstract

Vegf signaling specifies arterial fate during early vascular development by inducing the transcription of Delta-like 4 (Dll4), the earliest Notch ligand gene expressed in arterial precursor cells. Dll4 expression precedes that of Notch receptors in arteries, and factors that direct its arterial-specific expression are not known. To identify the transcriptional program that initiates arterial Dll4 expression, we characterized an arterial-specific and Vegf-responsive enhancer of Dll4. Our findings demonstrate that Notch signaling is not required for initiation of Dll4 expression in arteries and suggest that Notch instead functions as a maintenance factor. Importantly, we find that Vegf signaling activates MAP kinase (MAPK)-dependent E26 transformation-specific sequence (ETS) factors in the arterial endothelium to drive expression of Dll4 and Notch4. These findings identify a Vegf/MAPK-dependent transcriptional pathway that specifies arterial identity by activating Notch signaling components and illustrate how signaling cascades can modulate broadly expressed transcription factors to achieve tissue-specific transcriptional outputs.

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