Lipoprotein receptor signaling regulates the positioning and differentiation of postmitotic neurons during development and modulates neuronal plasticity in the mature brain. Depending on the contextual situation, the lipoprotein receptor ligand Reelin can have opposing effects on cortical neurons. We show that Reelin increases growth cone motility and filopodia formation, and identify the under...

The extracellular matrix molecule Reelin is known to control neuronal migration during development. Recent evidence suggests that it also plays a role in the maturation of postsynaptic dendrites and spines as well as in synaptic plasticity. Here, we aimed to address the question whether Reelin plays a role in presynaptic structural organization and function. Quantitative electron microscopic an...

During postnatal development, changes in the subunit composition of glutamate receptors of the NMDA subtype (NMDARs) are key to the refinement of excitatory synapses. Hypotheses for maturation of synaptic NMDARs include regulation of their expression levels, membrane targeting, and surface movements. In addition, several members of extracellular matrix (ECM) proteins such as Reelin are involved...

The developmental lamination of the hippocampus and other cortical structures requires a signaling cascade initiated by reelin and its receptors, apoER2 (apolipoprotein E receptor 2) and VLDLR (very-low-density lipoprotein receptor). However, the functional significance of continued reelin expression in the postnatal brain remains poorly understood. Here, we show that reelin application to adul...

Reelin is a large secreted glycoprotein that is essential for correct neuronal positioning during neurodevelopment and is important for synaptic plasticity in the mature brain. Moreover, Reelin is expressed in many extraneuronal tissues; yet the roles of peripheral Reelin are largely unknown. In the brain, many of Reelin's functions are mediated by a molecular signaling cascade that involves tw...

Reelin is a large extracellular glycoprotein required for proper neuronal positioning during development. In the adult brain, Reelin plays a crucial modulatory role in the induction of synaptic plasticity and successful formation of long-term memory. Recently, alterations in Reelin-mediated signaling have been suggested to contribute to neuronal dysfunction associated with Alzheimer's disease (...

Brain regions and neural circuits differ in their vulnerability to changes that occur during aging and in age-related neurodegenerative diseases. Among the areas that comprise the medial temporal lobe memory system, the layer II neurons of the entorhinal cortex, which form the perforant path input to the hippocampal formation, exhibit early alterations over the course of aging Reelin, a glycopr...

UNLABELLED How the integrity of laminar structures in the postnatal brain is maintained impacts neuronal functions. Ndel1, the mammalian homolog of NuDE from the filamentous fungus Aspergillus nidulans, is an atypical microtubule (MT)-associated protein that was initially investigated in the contexts of neurogenesis and neuronal migration. Constitutive knock-out mice for Ndel1 are embryonic let...

Disabled-1 (Dab1) is an adaptor protein that is an obligate effector of the Reelin signaling pathway, and is critical for neuronal migration and dendrite outgrowth during development. Components of the Reelin pathway are highly expressed during development, but also continue to be expressed in the adult brain. Here we investigated in detail the expression pattern of Dab1 in the postnatal and ad...

The extracellular protein Reelin is crucial for neuronal positioning during brain development, but its expression persists long after cell migration is completed. In this issue of Neuron, Beffert et al. demonstrate that Reelin exerts an additional function in the mature brain, to modulate synaptic plasticity and to favor memory formation. This activity is carried out exquisitely by the Apoer2 r...