Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2015 Jun 16;11(10):1577-90. doi: 10.1016/j.celrep.2015.05.018. Epub 2015 Jun 4.

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

Author information

1
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
2
UCL Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
3
UCL Division of Medicine, University College London, 5 University Street, London WC1E 6JJ, UK.
4
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK. Electronic address: c.ruhrberg@ucl.ac.uk.

Erratum in

  • Cell Rep. 2015 Dec 1;13(9):2037.

Abstract

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.

PMID:
26051942
PMCID:
PMC4528263
DOI:
10.1016/j.celrep.2015.05.018
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center