1999), three mutant mice show a remarkably similar cellular phenotype, suggesting that the corresponding proteins represent a biochemical pathway that mediates Lori Dulabon,*‖ Eric C. Olson,†‖ Mary G. Taglienti,‡ Scott Eisenhuth,* Barbara McGrath,* Christopher A. Walsh,† proper formation of cerebral cortical lamination. In the Jordan A. Kreidberg,‡ and E. S. Anton*§# reeler mouse, the disorgani...

The Reelin-Dab1 signaling pathway regulates development of the mammalian brain, including neuron migrations in various brain regions, as well as learning and memory in adults. Extracellular Reelin binds to cell surface receptors and activates phosphorylation of the intracellular Dab1 protein. Dab1 is required for most effects of Reelin, but Dab1-independent pathways may contribute. Here we deve...

The real role of reelin ttractants and repellents shunt neurons into their correct final location. But now Iris Hack, Harold Cremer (Université Mediterranée, Marseille, France), and colleagues have found evidence that reelin fits into neither of these categories. They propose, instead, that reelin converts cells that are migrating in association with each other into individual cells that can st...

The real role of reelin ttractants and repellents shunt neurons into their correct final location. But now Iris Hack, Harold Cremer (Université Mediterranée, Marseille, France), and colleagues have found evidence that reelin fits into neither of these categories. They propose, instead, that reelin converts cells that are migrating in association with each other into individual cells that can st...

Reelin is a large extracellular protein that controls cortical development. It binds to lipoprotein receptors very-low-density lipoprotein receptor and apolipoprotein-E receptor type 2, thereby inducing phosphorylation of the adapter Dab1. In vivo, Reelin is cleaved into three fragments, but their respective function is unknown. Here we show the following: (1) the central fragment is necessary ...

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...

Hepatocyte growth factor (HGF) and its receptor, c-Met, are widely expressed in the developing brain. HGF enhances cell proliferation and cell growth, stimulates cell migration and motility. Expression of mRNA for HGF has been seen in the rat brain. Neurons and glia produced in the neuroepithelium migrate along radial glial fibers into the cortical plate. Reelin, a glycoprotein which is produce...

The reeler gene encodes Reelin, a secreted glycoprotein that binds to the very-low-density lipoprotein receptor (Vldlr) and apolipoprotein E receptor 2 (Apoer 2), and induces Src- and Fyn-mediated tyrosine phosphorylation of the intracellular adaptor protein Disabled-1 (Dab1). This Reelin-Dab1 signaling pathway regulates neuronal positioning during development. A second Reelin pathway acts thro...