The alternative splicing factor Nova2 regulates vascular development and lumen formation

Costanza Giampietro, Gianluca Deflorian, Stefania Gallo, Anna Di Matteo, Davide Pradella, Serena Bonomi, Elisa Belloni, Daniel Nyqvist, Valeria Quaranta, Stefano Confalonieri, Giovanni Bertalot, Fabrizio Orsenigo, Federica Pisati, Elisabetta Ferrero, Giuseppe Biamonti, Evelien Fredrickx, Carla Taveggia, Chris D. R. Wyatt, Manuel Irimia, Pier Paolo Di Fiore, Benjamin J. Blencowe, Elisabetta Dejana () and Claudia Ghigna ()
Additional contact information
Costanza Giampietro: FIRC Institute of Molecular Oncology
Gianluca Deflorian: FIRC Institute of Molecular Oncology
Stefania Gallo: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche
Anna Di Matteo: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche
Davide Pradella: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche
Serena Bonomi: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche
Elisa Belloni: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche
Daniel Nyqvist: Karolinska Institutet
Valeria Quaranta: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche
Stefano Confalonieri: FIRC Institute of Molecular Oncology
Giovanni Bertalot: Istituto Europeo di Oncologia
Fabrizio Orsenigo: FIRC Institute of Molecular Oncology
Federica Pisati: FIRC Institute of Molecular Oncology
Elisabetta Ferrero: San Raffaele Scientific Institute
Giuseppe Biamonti: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche
Evelien Fredrickx: Division of Neuroscience and INSPE at San Raffaele Scientific Institute
Carla Taveggia: Division of Neuroscience and INSPE at San Raffaele Scientific Institute
Chris D. R. Wyatt: EMBL/CRG Research Unit in Systems Biology, Centre for Genomic Regulation (CRG)
Manuel Irimia: EMBL/CRG Research Unit in Systems Biology, Centre for Genomic Regulation (CRG)
Pier Paolo Di Fiore: FIRC Institute of Molecular Oncology
Benjamin J. Blencowe: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto
Elisabetta Dejana: FIRC Institute of Molecular Oncology
Claudia Ghigna: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms9479

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