Arterial branching morphogenesis

Branching is the key event in formation of vascular trees. Branching morphogenesis occurs not only during embryonic developments but also in adult tissues in response to a variety of signals such as organ growth, ischemia and tissue injury. Despite its obvious importance, little is known about signals inducing arterial branching, the intracellular signaling cascades responsible for it, or the cell types involved. While studying disruption of synectin gene expression, we noted, both in mice and in zebrafish models, significant abnormalities in arteriogenesis, including a reduction in the arterial tree size and a profound decrease in the number of arterial branches. Remarkably, neither venous nor lymphatic systems seem affected. Thus, it appears that synectin plays a key role in regulation of arterial differentiation as well branching. Molecular defects in synectin−/− endothelial cells include decreased responses to VEGF, FGF2 and PDGF stimulation, abnormal activation and mis‐localization of activated Rac1 and decreased Erk‐1/2 activation. The latter appears to be particularly important in regulation of arterial morphogenesis.