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Free keywords:
C3G; Ras signalling; vascular development; focal adhesions; integrins; PDGF
Abstract:
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-beta1-positive cell adhesions. In contrast, integrin-beta3-positive cell adhesions formed normally. These results show that C3G is required for (1) vascular myogenesis, (2) the formation of paxillin- and integrin beta1-positive, but not integrin beta3-positive, cell adhesions and (3) normal response to PDGF, necessary for vascular myogenesis.
