More than nervous: The emerging roles of plexins

Plexins are the receptors for semaphorins, a large family of axon guidance cues. Accordingly, the role of plexins in the development of the nervous system was the first to be acknowledged. However, the expression of plexins is not restricted to neuronal cells, and recent research has been increasingly focused on the roles of plexin–semaphorin signalling outside of the nervous system. During embryogenesis, plexins regulate the development of many organs, including the cardiovascular system, skeleton and kidney. They have also been shown to be involved in immune system functions and tumour progression. Analyses of the plexin signalling in different tissues and cell types have provided new insight to the versatility of plexin interactions with semaphorins and other cell-surface receptors. In this review we try to summarise the current understanding of the roles of plexins in non-neural development and immunity.

► A-plexins affect heart morphogenesis and are essential for bone homoeostasis.
► B-plexins regulate both angiogenesis and ureteric branching.
► Plexin D1 regulates vascular patterning and cardiac morphogenesis.
► Plexins A–D have many roles in immune cell maturation, migration and activation.
► Details of ligand binding are being dissected by analyses of crystallised complexes.