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*
- PubMed
- 23830865 Full text @ Dev. Cell
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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