Journal Article

Endothelial cell invasion is controlled by dactylopodia

Ferreira, Rita Rua, Vaccaro, Silvia, Ramalho, Daniela, Pena, Andreia, Lima, Aida Pires, Carvalho, Yulia, Vasconcelos, Francisca Ferreira, Franco, Claudio Areias, Russo, Ana, Barbacena, Pedro, Fidalgo, Marta Alves, Vignjevic, Danijela Matic, El-Marjou, Fatima, Lennon-Duménil, Ana-Maria, Figueiredo, Ana Martins

2021

Overview

Sprouting angiogenesis is fundamental for development and contributes to cancer, diabetic retinopathy, and cardiovascular diseases. Sprouting angiogenesis depends on the invasive properties of endothelial tip cells. However, there is very limited knowledge on how tip cells invade into tissues. Here, we show that endothelial tip cells use dactylopodia as the main cellular protrusion for invasion into nonvascular extracellular matrix. We show that dactylopodia and filopodia protrusions are balanced by myosin IIA (NMIIA) and actin-related protein 2/3 (Arp2/3) activity. Endothelial cell-autonomous ablation of NMIIA promotes excessive dactylopodia formation in detriment of filopodia. Conversely, endothelial cell-autonomous ablation of Arp2/3 prevents dactylopodia development and leads to excessive filopodia formation. We further show that NMIIA inhibits Rac1-dependent activation of Arp2/3 by regulating the maturation state of focal adhesions. Our discoveries establish a comprehensive model of how endothelial tip cells regulate its protrusive activity and will pave the way toward strategies to block invasive tip cells during sprouting angiogenesis.

• Publisher: National Academy of Sciences
• Subject: Ablation / Actin / Actin-related protein 2 / Angiogenesis / Biological Sciences / Cardiovascular diseases / Cell Biology / Diabetes mellitus / Diabetic retinopathy / Endothelial cells / Extracellular matrix / Filopodia / Invasiveness / Myosin / Rac1 protein / Retinopathy