Angiogenic morphogenesis driven by dynamic and heterogeneous collective endothelial cell movement

Area of Science:

• Cell Biology
• Developmental Biology
• Vascular Biology

Background:

• Angiogenesis, the formation of new blood vessels, involves complex cellular processes like sprouting and branching.
• The precise individual and collective behaviors of vascular endothelial cells (ECs) during this morphogenesis are not fully understood.

Purpose of the Study:

• To quantitatively characterize EC behaviors during sprouting angiogenesis using advanced imaging and analysis.
• To elucidate the mechanisms underlying collective cell movement and its role in vascular network formation.

Main Methods:

• Development of a time-lapse imaging and computer-assisted analysis system for quantitative behavioral characterization.
• Mosaic analysis to monitor individual EC behavior within multicellular structures.
• In vivo EC-tracking analysis in murine retinal vessels.

Main Results:

• Discovery of a dynamic "cell-mixing" phenomenon in ECs, including backward and forward movement and overtaking, even at the tip.
• Confirmation of "cell-mixing" at the whole-cell level and in vivo in developing retinal vessels.
• VEGF enhances tip cell behavior and stalk cell migration, modulated by Dll4-Notch signaling and EC-mural cell interactions.

Conclusions:

• Individual and collective EC movements, particularly "cell-mixing," are crucial for angiogenic morphogenesis.
• The developed methodology can bridge the understanding gap between single-cell behavior and complex vascular network development.