Regulation of Cortical Neuron Migration by the Reelin Signaling Pathway

Abstract

Reeler is a mutant mouse with defects in layered structures of the central nervous system, such as the cerebral cortex, hippocampus, and cerebellum, and has been extensively examined for more than half a century. The full-length cDNA for the responsible gene for reeler, reelin, was serendipitously identified, revealing that Reelin encodes a large secreted protein. So far, two Reelin receptors, apolipoprotein E receptor 2 and very low-density lipoprotein receptor, and the cytoplasmic adaptor protein Disabled homolog 1 (Dab1) have been shown to be essential for Reelin signaling. Although a number of downstream cascades of Dab1 have also been reported using various experimental systems, the physiological functions of Reelin in vivo remain controversial. Here, we review recent advances in the understanding of the Reelin-Dab1 signaling pathway in the developing cerebral cortex.

Common Partner Smad-Independent Canonical Bone Morphogenetic Protein Signaling in the Specification Process of the Anterior Rhombic Lip during Cerebellum Development

“…6I and J). This suggests that the amount of secreted reelin in the Smad1/5 mutant cerebellum was reduced and, thus, Dab-1 expression was upregulated due to a feedback mechanism (56,57). In addition, the expression of Lhx1 and Pax2 was investigated to determine if there was a defect in the specification and differentiation of Purkinje and GABAergic neuronal cells, respectively, arising from the ventricular zone in the Smad1/5 mutants (6, 11, 58-60).…”

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

“…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). Reelin also interacts directly with migrating neurons via a3b3 integrins (Dulabon et al, 2000).…”

“…Reelin also interacts directly with migrating neurons via a3b3 integrins (Dulabon et al, 2000). Reelin is supposed to influence cortical layering by serving as a stop signal that hinders migration and promotes detachment of migrating neurons from radial glial cells (Dulabon et al, 2000;Honda et al, 2011). In addition, it was proposed that a reelin/dab1-dependent stabilization of the leading process can also terminate migration in the MZ (Olson et al, 2006;Frotscher, 2010).…”

Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia

“…Importantly, other PNN elements, namely Reelin and semaphorin 3A, have been shown to be involved in the pathophysiology of SZ, although not directly as PNN components (Abdolmaleky et al, 2005a; Carulli et al, 2013a; Costa et al, 2001; Dick et al, 2013; Eastwood et al, 2003; Fatemi, 2005; Impagnatiello et al, 1998; Vo et al, 2013b). In particular, Reelin has been extensively investigated for its role in brain development, synaptic regulation during adulthood and involvement in several brain disorders, including SZ and bipolar disorder; although some of these aspects will be mentioned in this review, we refer to comprehensive publications by other groups for details (Abdolmaleky et al, 2005a; Akbarian and Huang, 2006; Barros et al, 2011; Campo et al, 2009; Chen et al, 2005; Costa et al, 2001; Curran and D’Arcangelo, 1998; Dityatev et al, 2006; Eastwood and Harrison, 2006; Fatemi, 2001; Flashner et al, 2013; Folsom and Fatemi, 2013; Franco and Muller, 2011; Frotscher, 2010; Frotscher et al, 2009a, b; Guidotti et al, 2011; Guidotti et al, 2000; Honda et al, 2011; Impagnatiello et al, 1998; Lakatosova and Ostatnikova, 2012; Pesold et al, 1999; Sinagra et al, 2005; Stranahan et al, 2013). …”