TY - JOUR
T1 - Sox17 is indispensable for acquisition and maintenance of arterial identity
AU - Corada, Monica
AU - Orsenigo, Fabrizio
AU - Morini, Marco Francesco
AU - Pitulescu, Mara Elena
AU - Bhat, Ganesh
AU - Nyqvist, Daniel
AU - Breviario, Ferruccio
AU - Conti, Valentina
AU - Briot, Anais
AU - Iruela-Arispe, M. Luisa
AU - Adams, Ralf H.
AU - Dejana, Elisabetta
N1 - Funding Information:
This work is supported by Grants from Fondation Leducq Transatlantic Network of Excellence, Associazione Italiana per la Ricerca sul Cancro (AIRC) and ‘Special Program Molecular Clinical Oncology 5 ⨯ 1,000’ to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative), the European Community (EUSTROKE-contract-202213; OPTIS-TEM-contract-223098; ENDOSTEM-HEALTH-2009-241440; JUSTBRAIN-HEALTH-2009-241861; ITN Vessels), the European Research Council (ERC) and CARIPLO Foundation. We are indebted with Dr S.J. Morrison and Dr D.A. Melton for generously sharing their genetically modified mouse strains.
PY - 2013
Y1 - 2013
N2 - The functional diversity of the arterial and venous endothelia is regulated through a complex system of signalling pathways and downstream transcription factors. Here we report that the transcription factor Sox17, which is known as a regulator of endoderm and hemopoietic differentiation, is selectively expressed in arteries, and not in veins, in the mouse embryo and in mouse postnatal retina and adult. Endothelial cell-specific inactivation of Sox17 in the mouse embryo is accompanied by a lack of arterial differentiation and vascular remodelling that results in embryo death in utero. In mouse postnatal retina, abrogation of Sox17 expression in endothelial cells leads to strong vascular hypersprouting, loss of arterial identity and large arteriovenous malformations. Mechanistically, Sox17 acts upstream of the Notch system and downstream of the canonical Wnt system. These data introduce Sox17 as a component of the complex signalling network that orchestrates arterial/venous specification.
AB - The functional diversity of the arterial and venous endothelia is regulated through a complex system of signalling pathways and downstream transcription factors. Here we report that the transcription factor Sox17, which is known as a regulator of endoderm and hemopoietic differentiation, is selectively expressed in arteries, and not in veins, in the mouse embryo and in mouse postnatal retina and adult. Endothelial cell-specific inactivation of Sox17 in the mouse embryo is accompanied by a lack of arterial differentiation and vascular remodelling that results in embryo death in utero. In mouse postnatal retina, abrogation of Sox17 expression in endothelial cells leads to strong vascular hypersprouting, loss of arterial identity and large arteriovenous malformations. Mechanistically, Sox17 acts upstream of the Notch system and downstream of the canonical Wnt system. These data introduce Sox17 as a component of the complex signalling network that orchestrates arterial/venous specification.
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U2 - 10.1038/ncomms3609
DO - 10.1038/ncomms3609
M3 - Article
C2 - 24153254
AN - SCOPUS:84886678124
SN - 2041-1723
VL - 4
JO - Nature communications
JF - Nature communications
M1 - 2609
ER -