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The alternative splicing factor Nova2 regulates vascular development and lumen formation
FIRC Inst Mol Oncol, I-20139 Milan, Italy.;Univ Milan, Dept Biosci, I-20133 Milan, Italy..
FIRC Inst Mol Oncol, I-20139 Milan, Italy..
CNR, Ist Genet Mol, I-27100 Pavia, Italy.;IUSS Ist Univ Super, I-27100 Pavia, Italy..
CNR, Ist Genet Mol, I-27100 Pavia, Italy.;Lazzaro Spallanzani Univ Pavia, Dipartimento Biol & Biotecnol, I-27100 Pavia, Italy..
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2015 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, 8479Article in journal (Refereed) Published
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Abstract [en]

Vascular lumen formation is a fundamental step during angiogenesis; yet, the molecular mechanisms underlying this process are poorly understood. Recent studies have shown that neural and vascular systems share common anatomical, functional and molecular similarities. Here we show that the organization of endothelial lumen is controlled at the post-transcriptional level by the alternative splicing (AS) regulator Nova2, which was previously considered to be neural cell-specific. Nova2 is expressed during angiogenesis and its depletion disrupts vascular lumen formation in vivo. Similarly, Nova2 depletion in cultured endothelial cells (ECs) impairs the apical distribution and the downstream signalling of the Par polarity complex, resulting in altered EC polarity, a process required for vascular lumen formation. These defects are linked to AS changes of Nova2 target exons affecting the Par complex and its regulators. Collectively, our results reveal that Nova2 functions as an AS regulator in angiogenesis and is a novel member of the 'angioneurins' family.

Place, publisher, year, edition, pages
2015. Vol. 6, 8479
National Category
Cardiac and Cardiovascular Systems
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URN: urn:nbn:se:uu:diva-269995DOI: 10.1038/ncomms9479ISI: 000364927100002PubMedID: 26446569OAI: oai:DiVA.org:uu-269995DiVA: diva2:885579
Funder
EU, European Research Council, EU-ERC 268870EU, European Research Council, ITN VESSEL 317250Swedish Research CouncilSwedish Society for Medical Research (SSMF)
Available from: 2015-12-19 Created: 2015-12-19 Last updated: 2017-12-01Bibliographically approved

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Di Fiore, Pier PaoloDejana, Elisabetta

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