Endothelial cell invasion is controlled by dactylopodia

Area of Science:

• Cell Biology
• Developmental Biology
• Cancer Biology

Background:

• Sprouting angiogenesis is vital for development and implicated in diseases like cancer and diabetic retinopathy.
• Endothelial tip cell invasion into tissues is critical for angiogenesis but poorly understood.
• Tip cells require invasive properties to navigate and form new blood vessels.

Purpose of the Study:

• To elucidate the cellular mechanisms and protrusions involved in endothelial tip cell invasion.
• To identify key molecular regulators balancing different cellular protrusions during invasion.
• To establish a model for tip cell protrusive activity in sprouting angiogenesis.

Main Methods:

• Investigated endothelial cell protrusions using genetic ablation of key proteins.
• Utilized techniques to assess dactylopodia and filopodia formation and balance.
• Examined the role of myosin IIA (NMIIA) and Arp2/3 complex in regulating cell invasion and focal adhesion maturation.

Main Results:

• Endothelial tip cells primarily use dactylopodia for invasion into nonvascular extracellular matrix.
• Myosin IIA (NMIIA) and Arp2/3 activity balance dactylopodia and filopodia formation.
• NMIIA deficiency leads to excessive dactylopodia, while Arp2/3 deficiency promotes filopodia.
• NMIIA regulates Rac1-dependent Arp2/3 activation via focal adhesion maturation.

Conclusions:

• Dactylopodia are the principal invasive protrusions of endothelial tip cells.
• A molecular balance involving NMIIA and Arp2/3 governs tip cell invasion.
• Understanding this regulation offers potential therapeutic targets for blocking aberrant angiogenesis.