The alternative splicing factor Nova2 regulates vascular development and lumen formation
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 organizati...
Saved in:
Published in | Nature communications Vol. 6; no. 1; p. 8479 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
08.10.2015
Nature Publishing Group Nature Pub. Group |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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.
The alternative splicing factor Nova2 is best known for its pivotal function in the brain. Giampietro
et al
. reveal an important role for Nova2 in the regulation of alternative splicing of transcripts in the vascular endothelium that are crucial for the maintenance of endothelial cell polarity and vessel lumen formation in zebrafish. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work These authors jointly supervised this work |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms9479 |