The gene mutated in reeler (reelin) encodes a protein secreted by neurons in the developing brain that controls laminar positioning of migrating cells in the CNS by an unknown mechanism. To investigate Reelin function, we used the nestin promoter to express Reelin ectopically in the ventricular zone and other brain regions in transgenic mice. In the presence of the endogenous protein, ectopic R...

Mutation of the reeler gene (Reln) disrupts neuronal migration in several brain regions and gives rise to functional deficits such as ataxic gait and trembling in the reeler mutant mouse. Thus, the Reln product, reelin, is thought to control cell-cell interactions critical for cell positioning in the brain. Although an abundance of reelin transcript is found in the embryonic spinal cord [Ikeda,...

Reln mRNA and protein levels are reduced by approximately 50% in various cortical structures of post-mortem brain from patients diagnosed with schizophrenia or bipolar illness with psychosis. To study mechanisms responsible for this down-regulation, we have analyzed the promoter of the human reelin gene. We show that the reelin promoter directs expression of a reporter construct in multiple hum...

Homozygous, loss-of-function mutations in the mouse Reelin gene cause a severe neurological phenotype known as reeler. These mutant mice exhibit marked cerebellar hypoplasia, dyslamination of cortical and hippocampal cellular layers, and malposition of specific neuronal populations in the brain stem and spinal cord. Similarly, homozygous mutations in the very conserved human REELIN gene cause a...

Reelin is an extracellular matrix protein that is crucial for neuron migration, adhesion, and positioning. We examined the expression of Reelin in a large cohort of multiple myeloma patients recorded in Gene Expression Omnibus (GEO) database and used over-expression and siRNA knockdown of Reelin to investigate the role of Reelin in myeloma cell growth. We find that Reelin expression is negative...

The reelin signaling protein and its downstream components have been associated with synaptic plasticity and neurotransmission. The reelin signaling pathway begins with the binding of reelin to the transmembrane lipoprotein receptor apolipoprotein E receptor 2 (ApoER2), which in turns induces the sequential cleavage of ApoER2 by the sequential action of α- and γ-secretases. Using conditional-kn...

Introduction Reelin, a gigantic extracellular glycoprotein, plays a central role in cortical layer formation during mammalian brain development. Reelin was originally identified as a gene product absent in reeler mice exhibiting malformations of the cerebral cortex. Reelin acts on migrating neuronal precursors, and regulates correct cell positioning in the cortex and other brain structures. It ...

Reelin is an extracellular signaling protein synthesized by Cajal-Retius cells in utero and early after birth, its presence being signaled in adult life too. Reelin acts on its receptors, VLDLR and ApoER2, acting on cytoskeleton, controlling migration and subsequently positioning and stabilizing the cortical neurons. We investigated the reelin presence and its receptors, VLDLR and ApoER2, in me...

Early life stress predisposes to the development of psychiatric disorders. In this context the hippocampal formation is of particular interest, because it is affected by stress on the structural and cognitive level. Since little is known how early life stress is translated on the molecular level, we mimicked early life stress in mouse models and analyzed the expression of the glycoprotein Reeli...

BDNF positively influences various aspects of neuronal migration, maturation, and survival in the developing brain. Reelin in turn mediates inhibitory signals to migrating neuroblasts, which is crucial for brain development. The interplay between BDNF and Reelin signaling in neurodevelopment is not fully understood. We show here that BDNF increased the levels of the Reelin receptor (VLDL recept...