Author
Listed:
- Costanza Giampietro
(FIRC Institute of Molecular Oncology
Milan University)
- Gianluca Deflorian
(FIRC Institute of Molecular Oncology)
- Stefania Gallo
(Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche
IUSS—Istituto Universitario di Studi Superiori)
- Anna Di Matteo
(Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche
`Lazzaro Spallanzani' - Università degli Studi di Pavia)
- Davide Pradella
(Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche
`Lazzaro Spallanzani' - Università degli Studi di Pavia)
- 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
Istituto Europeo di Oncologia)
- 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)
Universitat Pompeu Fabra (UPF))
- Manuel Irimia
(EMBL/CRG Research Unit in Systems Biology, Centre for Genomic Regulation (CRG)
Universitat Pompeu Fabra (UPF))
- Pier Paolo Di Fiore
(FIRC Institute of Molecular Oncology
Istituto Europeo di Oncologia
University of Milan)
- Benjamin J. Blencowe
(Donnelly Centre for Cellular and Biomolecular Research, University of Toronto)
- Elisabetta Dejana
(FIRC Institute of Molecular Oncology
Milan University
Rudbeck Laboratory and Science for Life Laboratory, Genetics and Pathology, Uppsala University)
- Claudia Ghigna
(Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche)
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.
Suggested Citation
Costanza Giampietro & Gianluca Deflorian & Stefania Gallo & Anna Di Matteo & Davide Pradella & Serena Bonomi & Elisa Belloni & Daniel Nyqvist & Valeria Quaranta & Stefano Confalonieri & Giovanni Berta, 2015.
"The alternative splicing factor Nova2 regulates vascular development and lumen formation,"
Nature Communications, Nature, vol. 6(1), pages 1-15, December.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9479
DOI: 10.1038/ncomms9479
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