Reelin signaling in development, maintenance, and plasticity of neural networks

The developing brain is formed through an orchestrated pattern of neuronal migration, leading to the formation of heterogeneous functional regions in the adult. Several proteins and pathways have been identified as mediators of developmental neuronal migration and cell positioning. However, these pathways do not cease to be functionally relevant after the embryonic and early postnatal period; instead, they switch from guiding cells, to guiding synapses. The outcome of synaptic guidance determines the strength and plasticity of neuronal networks by creating a scalable functional architecture that is sculpted by cues from the internal and external environment. Reelin is a multifunctional signal that coordinates cortical and subcortical morphogenesis during development and regulates structural plasticity in adulthood and aging. Gain or loss of function in reelin or its receptors has the potential to influence synaptic strength and patterns of connectivity, with consequences for memory and cognition. The current review highlights similarities in the signaling cascades that modulate neuronal positioning during development, and synaptic plasticity in the adult, with a focus on reelin, a glycoprotein that is increasingly recognized for its dual role in the formation and maintenance of neural circuits.