Sox18 genetically interacts With VegfC to regulate lymphangiogenesis in zebrafish

Cermenati, Solei, Moleri, Silvia, Neyt, Christine, Bresciani, Erica, Carra, Silvia, Grassini, Daniela R., Omini, Alice, Goi, Michela, Cotelli, Franco, François, Mathias, Hogan, Benjamin M. and Beltrame, Monica (2013) Sox18 genetically interacts With VegfC to regulate lymphangiogenesis in zebrafish. Arteriosclerosis, Thrombosis and Vascular Biology, 33 6: 1238-1247. doi:10.1161/ATVBAHA.112.300254

Author Cermenati, Solei
Moleri, Silvia
Neyt, Christine
Bresciani, Erica
Carra, Silvia
Grassini, Daniela R.
Omini, Alice
Goi, Michela
Cotelli, Franco
François, Mathias
Hogan, Benjamin M.
Beltrame, Monica
Title Sox18 genetically interacts With VegfC to regulate lymphangiogenesis in zebrafish
Journal name Arteriosclerosis, Thrombosis and Vascular Biology   Check publisher's open access policy
ISSN 1079-5642
Publication date 2013-06
Sub-type Article (original research)
DOI 10.1161/ATVBAHA.112.300254
Volume 33
Issue 6
Start page 1238
End page 1247
Total pages 37
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Collection year 2014
Language eng
Formatted abstract
Objective—Lymphangiogenesis is regulated by transcription factors and by growth factor pathways, but their interplay has not been extensively studied so far. We addressed this issue in zebrafish.

Approach and Results—Mutations in the transcription factor–coding gene SOX18 and in VEGFR3 cause lymphedema, and the VEGFR3/Flt4 ligand VEGFC plays an evolutionarily conserved role in lymphangiogenesis. Here, we report a strong genetic interaction between Sox18 and VegfC in the early phases of lymphatic development in zebrafish. Knockdown of sox18 selectively impaired lymphatic sprouting from the cardinal vein and resulted in defective lymphatic thoracic duct formation. Sox18 and the related protein Sox7 play redundant roles in arteriovenous differentiation. We used a novel transgenic line that enables inducible expression of a dominant-negative mutant form of mouse Sox18 protein. Our data led us to conclude that Sox18 is crucially involved in lymphangiogenesis after arteriovenous differentiation. Combined partial knockdown of sox18 and vegfc, using subcritical doses of specific morpholinos, revealed a synergistic interaction in both venous and lymphatic sprouting from the cardinal vein and greatly impaired thoracic duct formation.

Conclusions—This interaction suggests a previously unappreciated crosstalk between the growth factor and transcription factor pathways that regulate lymphangiogenesis in development and disease.
Keyword Lymphangiogenesis
Sox transcription factors
Vascular development
Lymphatic endothelial-cells
Vascular development
Embryonic lymphangiogenesis
Transcription factor
Primary lymphedema
Transgenic zebrafish
Redundant roles
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 19 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 07 Jul 2013, 00:28:19 EST by System User on behalf of Institute for Molecular Bioscience