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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Vascular Biology

Background:

  • Angiogenesis involves vascular tip cells guiding new blood vessel formation.
  • Apelin, a ligand for Aplnr, is found in vascular tip cells, suggesting a role in regulating sprouting angiogenesis.
  • The source and precise function of Apelin in angiogenesis remain incompletely understood.

Purpose of the Study:

  • To investigate the role of Apelin in regulating vascular tip cell behavior during sprouting angiogenesis.
  • To identify the cellular source of Apelin that influences angiogenesis.
  • To elucidate the signaling pathways modulated by Apelin in tip cells.

Main Methods:

  • Identification of Apelin-expressing cells in the dorsal neural tube.
  • Analysis of vascular tip cell migration and elongation in Apelin-deficient models.
  • Genetic manipulation to restore Apelin expression in neural or vascular compartments.
  • Functional assays to assess tip cell behaviors (e.g., filopodia formation).
  • Genetic interaction studies and analysis of signaling pathway reporters (PI3K, ERK).

Main Results:

  • A population of Apelin-expressing neural progenitor cells was identified.
  • Vascular tip cells migrated towards and along these neural progenitor cells.
  • Restoring neural Apelin expression, but not vascular, rescued angiogenic defects in mutants.
  • Apelin signaling is required for tip cell elongation and filopodia formation.
  • Apelin signaling modulates phosphoinositide 3-kinase and extracellular signal-regulated kinase pathways in tip cells.

Conclusions:

  • Apelin signaling, originating from neural progenitor cells, is critical for vascular tip cell function during sprouting angiogenesis.
  • This study reveals a novel neurovascular cross-talk mechanism mediated by Apelin.
  • Apelin's role in modulating PI3K/ERK signaling is essential for tip cell behavior in vivo.