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doi: 10.1242/10.1242/dev.00217

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The guanine nucleotide exchange factor C3G is necessary for the formation of focal adhesions and vascular maturation

¹ Development and Neurobiology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
² Max-Planck-Institute of Biophysical Chemistry, Goettingen, Germany

^* Author for correspondence (e-mail: avoss{at}wehi.edu.au)

Accepted 11 October 2002

The Ras signalling pathway has major roles in normal cell function and oncogenesis. C3G is a guanine nucleotide exchange factor for members of the Ras family of GTPases. We generated a mouse strain with a hypomorphic C3G allele. C3G^gt/gt mutant embryos died of vascular defects around E11.5 due to haemorrhage and vascular integrity defects. Vascular supporting cells did not develop appropriately. C3G-deficient fibroblasts responded to PDGF-BB abnormally, exhibited cell adhesion defects and lacked paxillin and integrin-ß1-positive cell adhesions. In contrast, integrin-ß3-positive cell adhesions formed normally. These results show that C3G is required for (1) vascular myogenesis, (2) the formation of paxillin- and integrin ß1-positive, but not integrin ß3-positive, cell adhesions and (3) normal response to PDGF, necessary for vascular myogenesis.

Key words: C3G, Ras signalling, Vascular development, Focal adhesions, Integrins, PDGF

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