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The alternative splicing factor Nova2 regulates vascular development and lumen formation.

Costanza Giampietro1,2, Gianluca Deflorian1, Stefania Gallo3,4

  • 1FIRC Institute of Molecular Oncology, Via Adamello 16, Milan 20139, Italy.

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Nova2, a neural regulator, controls blood vessel lumen formation by altering endothelial cell polarity through alternative splicing. This finding reveals Nova2

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Background:

  • Vascular lumen formation is crucial for angiogenesis but poorly understood.
  • Neural and vascular systems share similarities, suggesting common regulatory mechanisms.

Purpose of the Study:

  • To investigate the role of the alternative splicing regulator Nova2 in vascular lumen formation.
  • To explore the molecular mechanisms by which Nova2 influences endothelial cell polarity.

Main Methods:

  • In vivo studies of Nova2 depletion during angiogenesis.
  • In vitro experiments using cultured endothelial cells (ECs).
  • Analysis of alternative splicing events and Par polarity complex signaling.

Main Results:

  • Nova2 is expressed during angiogenesis and its depletion disrupts vascular lumen formation.
  • Nova2 depletion in ECs impairs apical distribution and signaling of the Par polarity complex.
  • Defects are linked to Nova2-mediated alternative splicing changes in Par complex components.

Conclusions:

  • Nova2 regulates endothelial lumen organization at the post-transcriptional level.
  • Nova2 functions as an alternative splicing regulator in angiogenesis.
  • Nova2 is identified as a novel member of the 'angioneurins' family.