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

Abstract

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 ageing. 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.

NGF Expression in Reelin-Deprived Retinal Cells: A Potential Neuroprotective Effect

“…Reelin is upregulated during development, deregulated at adulthood and significantly increased upon injury (Pulido et al 2007;Förster et al 2010). Chiefly Reelin takes part in the migration of several neuronal and non-neuronal cell types, showing some cell activities common to other soluble mediators and pleiotropic factors such as the nerve growth factor (NGF) (Khialeeva et al 2011;Stranahan et al 2013). Old and recent data support the involvement of NGF in developing and maintenance of the visual system (Micera et al 2006;Aloe et al 2008).…”

Cajal–Retzius cells: Update on structural and functional properties of these mystic neurons that bridged the 20th century

“…Beside their postulated role in controlling electrical activity in terminal tufts of dendrites, the main function assigned to CRc is their direct implication to cortical layering via reelin release (Frotscher, 1998(Frotscher, , 2010Stranahan et al, 2013). Reelin acts mainly via binding to the VLDL-and the ApoR2-receptors which act via the adaptor protein dab1 on various molecular downstream targets (Hiesberger et al, 1999;Frotscher, 2010;Honda et al, 2011).…”

Heterozygous Reelin Mutations Cause Autosomal-Dominant Lateral Temporal Epilepsy

“…[46][47][48] Phosphorylated DAB1 activates several different signaling pathways involved in formation and plasticity of neuronal networks (for review, see ref. 49 ). Recent work on conditional knockout mice suggests that LGI1, like Reelin, could serve different functions during brain development and adulthood.…”