Publication: Analysis of Dll4 regulation reveals a combinatorial rolefor Sox and Notch in arterial development
Loading...
Date
2013-07-01
Authors
Sacilotto, Natalia ; Monteiro, Rui ; Fritzsche, Martin ; Becker, Philipp W. ; Liu, Ke ; Pinheiro, Philip ; Ratnayakaa, Indrika ; Davies, Benjamin ; Goding, Colin R. ; Patient, Roger ; Bou Gharios, George ; De Val, Sarah ; Sánchez del Campo Ferrer, Luis
item.page.secondaryauthor
item.page.director
Publisher
National Academy of Sciences
publication.page.editor
publication.page.department
DOI
https://doi.org/10.1073/pnas.1300805110
item.page.type
info:eu-repo/semantics/article
Description
© 2013 National Academy of Sciences. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This document is the Published version of a Published Work that appeared in final form in PNAS. To access the final edited and published work see https://doi.org/10.1073/pnas.1300805110
Abstract
The mechanisms by which arterial fate is established and main-tained are not clearly understood. Although a number of signalingpathways and transcriptional regulators have been implicated inarterio-venous differentiation, none are essential for arterialformation, and the manner in which widely expressed factorsmay achieve arterial-specific gene regulation is unclear. Using bothmouse and zebrafish models, we demonstrate here that arterialspecification is regulated combinatorially by Notch signaling andSoxF transcription factors, via direct transcriptional gene activa-tion. Through the identification and characterization of two arte-rial endothelial cell-specific gene enhancers for the Notch ligandDelta-like ligand 4 (Dll4), we show that arterial Dll4 expressionrequires the direct binding of both the RBPJ/Notch intracellulardomain and SOXF transcription factors. Specific combinatorial,but not individual, loss of SOXF and RBPJ DNA binding ablatesall Dll4 enhancer-transgene expression despite the presence ofmultiple functional ETS binding sites, as does knockdown of sox7;sox18 in combination with loss of Notch signaling. Furthermore,triple knockdown of sox7, sox18 and rbpj also results in ablationof endogenous dll4 expression. Fascinatingly, this combinatorialablation leads to a loss of arterial markers and the absence of a de-tectable dorsal aorta, demonstrating the essential roles of SoxF andNotch, together, in the acquisition of arterial identity
publication.page.subject
Citation
Proceedings of the National Academy of Sciences (PNAS), 2013, Vol. 110, N. 29, pp. 11893–11898
item.page.embargo
Collections
Ir a Estadísticas
Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/