Neural progenitor-derived Apelin controls tip cell behavior and vascular patterning.

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.