title: The alternative splicing factor Nova2 regulates vascular development and lumen formation.
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.
authors.affiliation: FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy.|Department of Biosciences, Milan University, Via Celoria 26, Milan 20133, Italy.
authors.forename: Costanza
authors.initials: C
authors.lastname: Giampietro
authors.affiliation: FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Deflorian
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, Pavia 27100, Italy.|IUSS-Istituto Universitario di Studi Superiori, Piazza della Vittoria 15, Pavia 27100, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gallo
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, Pavia 27100, Italy.|Dipartimento di Biologia e Biotecnologie, `Lazzaro Spallanzani' - Università degli Studi di Pavia, via Ferrata 9, Pavia 27100, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Matteo
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, Pavia 27100, Italy.|Dipartimento di Biologia e Biotecnologie, `Lazzaro Spallanzani' - Università degli Studi di Pavia, via Ferrata 9, Pavia 27100, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Pradella
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, Pavia 27100, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Bonomi
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, Pavia 27100, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Belloni
authors.affiliation: Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Daniel
authors.identifier: http://orcid.org/0000-0002-6527-6716
authors.initials: D
authors.lastname: Nyqvist
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, Pavia 27100, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Quaranta
authors.affiliation: FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy.|Dipartimento di Oncologia Sperimentale, Istituto Europeo di Oncologia, Milan 20141, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Confalonieri
authors.affiliation: Dipartimento di Oncologia Sperimentale, Istituto Europeo di Oncologia, Milan 20141, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Bertalot
authors.affiliation: FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Orsenigo
authors.affiliation: FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Pisati
authors.affiliation: Department of Oncology, San Raffaele Scientific Institute, via Olgettina 58, Milan 20132, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferrero
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, Pavia 27100, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biamonti
authors.affiliation: Division of Neuroscience and INSPE at San Raffaele Scientific Institute, via Olgettina 58, Milan 20132, Italy.
authors.forename: Evelien
authors.initials: E
authors.lastname: Fredrickx
authors.affiliation: Division of Neuroscience and INSPE at San Raffaele Scientific Institute, via Olgettina 58, Milan 20132, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Taveggia
authors.affiliation: EMBL/CRG Research Unit in Systems Biology, Centre for Genomic Regulation (CRG), Barcelona 08003, Spain.|Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain.
authors.forename: Chris D R
authors.initials: CD
authors.lastname: Wyatt
authors.affiliation: EMBL/CRG Research Unit in Systems Biology, Centre for Genomic Regulation (CRG), Barcelona 08003, Spain.|Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Irimia
authors.affiliation: FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy.|Dipartimento di Oncologia Sperimentale, Istituto Europeo di Oncologia, Milan 20141, Italy.|Dipartimento di Scienze della Salute, University of Milan, Milan 20122, Italy.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario, Canada M5S 3E1.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Blencowe
authors.affiliation: FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy.|Department of Biosciences, Milan University, Via Celoria 26, Milan 20133, Italy.|Rudbeck Laboratory and Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Dag Hammarksjöldsv 20, Uppsala 751 85, Sweden.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dejana
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, Pavia 27100, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Ghigna
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D000090682:Neuro-Oncological Ventral Antigen; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D000090682:Neuro-Oncological Ventral Antigen; C515624:Nova2 protein, mouse; D016601:RNA-Binding Proteins