PUBLICATION
Sox18 and Sox7 play redundant roles in vascular development
- Authors
- Cermenati, S., Moleri, S., Cimbro, S., Corti, P., Del Giacco, L., Amodeo, R., Dejana, E., Koopman, P., Cotelli, F., and Beltrame, M.
- ID
- ZDB-PUB-071227-7
- Date
- 2008
- Source
- Blood 111(5): 2657-2666 (Journal)
- Registered Authors
- Beltrame, Monica, Cotelli, Franco, Del Giacco, Luca
- Keywords
- none
- MeSH Terms
-
- Sequence Homology, Amino Acid
- Biomarkers/metabolism
- Animals, Genetically Modified
- Organ Specificity
- Endothelial Cells/metabolism
- PubMed
- 18094332 Full text @ Blood
Abstract
Mutations in SOX18 cause the human Hypotrichosis-Lymphedema-Telangiectasia (HLT) syndrome. Their murine counterparts are the spontaneous ragged mutants, showing combined defects in hair follicle, blood vessel and lymphatic vessel development. Mice null for Sox18 display only mild coat defects, suggesting a dominant negative effect of Sox18/ragged mutations and functional redundancy between Sox18 and other Sox-F proteins. We addressed this point in zebrafish. The zebrafish homologues of Sox18 and of Sox7 are expressed in angioblasts and in the endothelial component of nascent blood vessels in embryos. Knockdown of either gene, using moderate doses of specific morpholinos, had minimal effects on vessels. In contrast, simultaneous knockdown of both genes resulted in multiple fusions between the major axial vessels. With combined use of transgenic lines and molecular markers, we could show that endothelial cells are specified, but fail to acquire a correct arteriovenous identity. Venous endothelial cell differentiation was more severely affected than arterial. Thus, sox7 and sox18 play redundant but collectively essential roles in the establishment of proper arteriovenous identity in zebrafish. Our data suggest that a defect in arteriovenous identity could be responsible for the formation of telangiectases in HLT patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping