Reelin functions beyond neuronal migration: from synaptogenesis to network activity modulation.

Reelin, a glycoprotein of the extracellular matrix, has been the focus of several studies over the years, mostly for its role in cell migration. Here we report the role of this molecule and of its downstream pathways in post-mitotic neurons and how they contribute to neural circuit assembly, refinement and function. Accumulating evidence has pointed at a major role for Reelin in axonal guidance, synaptogenesis and dendritic spine formation. In particular, new evidence points at a direct role in axonal targeting and refinement at the target site. In addition, recent advances highlight new functions of Reelin in the modulation of synaptic activity, plasticity and behavior and in the direct regulation of GABA receptors expression and stability. We discuss these findings in the context of neurodevelopmental disorders.