Integrin activity in neuronal connectivity

The formation of correct synaptic structures and neuronal connections is paramount for normal brain development and a functioning adult brain. The integrin family of cell adhesion receptors and their ligands play essential roles in the control of several processes regulating neuronal connectivity - including neurite outgrowth, the formation and maintenance of synapses, and synaptic plasticity - that are affected in neurodevelopmental disorders, such as autism spectrum disorders (ASDs) and schizophrenia. Many ASD- and schizophrenia-associated genes are linked to alterations in the genetic code of integrins and associated signalling pathways. In non-neuronal cells, crosstalk between integrin-mediated adhesions and the actin cytoskeleton, and the regulation of integrin activity (affinity for extracellular ligands) are widely studied in healthy and pathological settings. In contrast, the roles of integrin-linked pathways in the central nervous system remains less well defined. In this Review, we will provide an overview of the known pathways that are regulated by integrin-ECM interaction in developing neurons and in adult brain. We will also describe recent advances in the identification of mechanisms that regulate integrin activity in neurons, and highlight the interesting emerging links between integrins and neurodevelopment.