| First Author | Wythe JD | Year | 2013 |
| Journal | Dev Cell | Volume | 26 |
| Issue | 1 | Pages | 45-58 |
| PubMed ID | 23830865 | Mgi Jnum | J:297694 |
| Mgi Id | MGI:6479161 | Doi | 10.1016/j.devcel.2013.06.007 |
| Citation | Wythe JD, et al. (2013) ETS factors regulate Vegf-dependent arterial specification. Dev Cell 26(1):45-58 |
| abstractText | 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. |
