VEGFD regulates blood vascular development by modulating SOX18 activity

Duong, Tam, Koltowska, Katarzyna, Pichol-Thievend, Cathy, Le Guen, Ludovic, Fontaine, Frank R., Smith, Kelly, Truong, Vy, Skoczylas, Renae, Stacker, Steven A., Achen, Marc G., Koopman, Peter, Hogan, Ben and Francois, Mathias (2013) VEGFD regulates blood vascular development by modulating SOX18 activity. Blood, 123 7: 1102-1112. doi:10.1182/blood-2013-04-495432

Author Duong, Tam
Koltowska, Katarzyna
Pichol-Thievend, Cathy
Le Guen, Ludovic
Fontaine, Frank R.
Smith, Kelly
Truong, Vy
Skoczylas, Renae
Stacker, Steven A.
Achen, Marc G.
Koopman, Peter
Hogan, Ben
Francois, Mathias
Title VEGFD regulates blood vascular development by modulating SOX18 activity
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2013-11-22
Year available 2013
Sub-type Article (original research)
DOI 10.1182/blood-2013-04-495432
Volume 123
Issue 7
Start page 1102
End page 1112
Total pages 11
Place of publication Washington, United States
Publisher American Society of Hematology
Language eng
Formatted abstract
Vascular endothelial growth factor-D (VEGFD) is a potent pro-lymphangiogenic molecule of tumour growth and is considered a key therapeutic target to modulate metastasis. Despite roles in pathological neo-lymphangiogenesis, the characterisation of an endogenous role for VEGFD in vascular development has remained elusive. Here, we used zebrafish to assay for genetic interactions between the Vegf/Vegf-receptor pathway and SoxF transcription factors and identified a specific interaction between Vegfd and Sox18. Double knockdown zebrafish embryos for Sox18/Vegfd and Sox7/Vegfd exhibit defects in arteriovenous differentiation. Supporting this observation, we found that Sox18/Vegfd double but not single knockout mice displayed dramatic vascular development defects. We find that VEGFD-MEK-ERK signalling modulates SOX18-mediated transcription, functioning at least in part by enhancing nuclear concentration and transcriptional activity in vascular endothelial cells. This work suggests that VEGFD-mediated pathologies include or involve an underlying dysregulation of SOXF-mediated transcriptional networks.
Keyword Sox18
Blood vessel
Arteriovenous differentiation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 22 November 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 21 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 23 times in Scopus Article | Citations
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Created: Wed, 11 Dec 2013, 22:03:34 EST by Susan Allen on behalf of Institute for Molecular Bioscience