Mutations in SOX18 cause the human hypotrichosis-lymphedema-telangiectasia (HILT) syndrome. Their murine counterparts are the spontaneous raggedmutants, 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 homologs 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 patients with HLT.

Sox18 and Sox7 play redundant roles in vascular development / S. Cermenati, S. Moleri, S. Cimbro, P. Corti, L. Del Giacco, R. Amodeo, E. Dejana, P. Koopman, F. Cotelli, M. Beltrame. - In: BLOOD. - ISSN 0006-4971. - 111:5(2008), pp. 2657-2666.

Sox18 and Sox7 play redundant roles in vascular development

S. Cermenati;S. Moleri;S. Cimbro;P. Corti;L. Del Giacco;E. Dejana;F. Cotelli;M. Beltrame
2008

Abstract

Mutations in SOX18 cause the human hypotrichosis-lymphedema-telangiectasia (HILT) syndrome. Their murine counterparts are the spontaneous raggedmutants, 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 homologs 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 patients with HLT.
Settore MED/04 - Patologia Generale
Settore BIO/06 - Anatomia Comparata e Citologia
Settore BIO/18 - Genetica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/36579
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