During organogenesis, mechanical forces can induce transcriptional and cytoskeletal changes in cells that help shape tissues as they develop. However, the mechanisms allowing cells to sense and respond to these mechanical signals are poorly understood. In the cardiovascular system, endothelial cells, which line the arteries, are able to change their shape in response to high or low blood flow through an artery, resulting in a change to the vessel’s diameter. On p. 3241, Kristy Red-Horse and colleagues investigate how mechanical signals are transduced by endothelial cells to regulate the size of arteries, and show that SMAD4 signalling mediates this response. When SMAD4 is deleted in mice, coronary artery size is increased, subsequent to the onset of blood flow. They also show that in human coronary artery endothelial cells cultured in vitro, knockdown of SMAD4 leads to defects in flow-guided cell elongation and migration. Additionally, they find that these cells undergo increased proliferation when exposed to shear stress. Their data directly link BMP/SMAD signalling to endothelial changes in response to mechanical force. These results increase our understanding of how forces can regulate tissue development during embryogenesis, and might be important in developing treatments for human vascular pathologies.