UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Crim1 maintains retinal vascular stability during development by regulating endothelial cell Vegfa autocrine signaling

Fan, J; Ponferrada, VG; Sato, T; Vemaraju, S; Fruttiger, M; Gerhardt, H; Ferrara, N; (2014) Crim1 maintains retinal vascular stability during development by regulating endothelial cell Vegfa autocrine signaling. Development , 141 (2) , Article dev.097949. 10.1242/dev.097949. Green open access

[img]
Preview
PDF
Development-2014-Fan-448-59.pdf
Available under License : See the attached licence file.

Download (9MB)
[img]
Preview
PDF (DEV097949 Supplementary Materia)
DEV097949.pdf

Download (6MB)

Abstract

Angiogenesis defines the process in which new vessels grow from existing vessels. Using the mouse retina as a model system, we show that cysteine-rich motor neuron 1 (Crim1), a type I transmembrane protein, is highly expressed in angiogenic endothelial cells. Conditional deletion of the Crim1 gene in vascular endothelial cells (VECs) causes delayed vessel expansion and reduced vessel density. Based on known Vegfa binding by Crim1 and Crim1 expression in retinal vasculature, where angiogenesis is known to be Vegfa dependent, we tested the hypothesis that Crim1 is involved in the regulation of Vegfa signaling. Consistent with this hypothesis, we showed that VEC-specific conditional compound heterozygotes for Crim1 and Vegfa exhibit a phenotype that is more severe than each single heterozygote and indistinguishable from that of the conditional homozygotes. We further showed that human CRIM1 knockdown in cultured VECs results in diminished phosphorylation of VEGFR2, but only when VECs are required to rely on an autocrine source of VEGFA. The effect of CRIM1 knockdown on reducing VEGFR2 phosphorylation was enhanced when VEGFA was also knocked down. Finally, an anti-VEGFA antibody did not enhance the effect of CRIM1 knockdown in reducing VEGFR2 phosphorylation caused by autocrine signaling, but VEGFR2 phosphorylation was completely suppressed by SU5416, a small-molecule VEGFR2 kinase inhibitor. These data are consistent with a model in which Crim1 enhances the autocrine signaling activity of Vegfa in VECs at least in part via Vegfr2.

Type: Article
Title: Crim1 maintains retinal vascular stability during development by regulating endothelial cell Vegfa autocrine signaling
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.097949
Publisher version: http://dx.doi.org/10.1242/dev.097949
Language: English
Additional information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1417942
Downloads since deposit
182Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item