Semaphorins in development and adult brain: Implication for neurological diseases

As a group, Semaphorins are expressed in most tissues and this distribution varies considerably with age. Semaphorins are dynamically expressed during embryonic development and their expression is often associated with growing axons. This expression decreases with maturity and several observations support the idea that in adult brain the expression of secreted Semaphorins is sensitive to electrical activity and experience. The functional role of Semaphorins in guiding axonal projections is well established and more recent evidence points to additional roles in the development, function and reorganization of synaptic complexes. Semaphorins exert the majority of their effects by binding to cognate receptor proteins through their extracellular domains. A common theme is that Semaphorin-triggered signalling induces the rearrangement of the actin and microtubule cytoskeleton. Mutations in Semaphorin genes are linked to several human diseases associated with neurological changes, but their actual influence in the pathogenesis of these diseases remains to be demonstrated. In addition, Semaphorins and their receptors are likely to mediate cross-talk between neurons and other cell types, including in pathological situations where their influence can be damaging or favourable depending on the context. We discuss how the manipulation of Semaphorin function might be crucial for future clinical studies.