ZFIN ID: ZDB-PUB-130729-1
ETS Factors Regulate Vegf-Dependent Arterial Specification
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.
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
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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.

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