NRP1 Regulates CDC42 Activation to Promote Filopodia Formation in Endothelial Tip Cells

被引:81
作者
Fantin, Alessandro [1 ]
Lampropoulou, Anastasia [1 ]
Gestri, Gaia [2 ]
Raimondi, Claudio [1 ]
Senatore, Valentina [1 ]
Zachary, Ian [3 ]
Ruhrberg, Christiana [1 ]
机构
[1] UCL, UCL Inst Ophthalmol, London EC1V 9EL, England
[2] UCL, UCL Dept Cell & Dev Biol, London WC1E 6BT, England
[3] UCL, UCL Div Med, London WC1E 6JJ, England
来源
CELL REPORTS | 2015年 / 11卷 / 10期
基金
英国惠康基金; 英国医学研究理事会;
关键词
EMBRYONIC VASCULAR DEVELOPMENT; RHOMBOMERE BOUNDARIES; DEVELOPING ZEBRAFISH; GROWTH-FACTOR; IN-VIVO; ANGIOGENESIS; VEGF; NEUROPILIN-1; BINDING; HINDBRAIN;
D O I
10.1016/j.celrep.2015.05.018
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Sprouting blood vessels are led by filopodia-studded endothelial tip cells that respond to angiogenic signals. Mosaic lineage tracing previously revealed that NRP1 is essential for tip cell function, although its mechanistic role in tip cells remains poorly defined. Here, we show that NRP1 is dispensable for genetic tip cell identity. Instead, we find that NRP1 is essential to form the filopodial bursts that distinguish tip cells morphologically from neighboring stalk cells, because it enables the extracellular matrix (ECM)-induced activation of CDC42, a key regulator of filopodia formation. Accordingly, NRP1 knockdown and pharmacological CDC42 inhibition similarly impaired filopodia formation in vitro and in developing zebrafish in vivo. During mouse retinal angiogenesis, CDC42 inhibition impaired tip cell and vascular network formation, causing defects that resembled those due to loss of ECM-induced, but not VEGF-induced, NRP1 signaling. We conclude that NRP1 enables ECM-induced filopodia formation for tip cell function during sprouting angiogenesis.
引用
收藏
页码:1577 / 1590
页数:14
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