Downregulation of functional Reelin receptors in projection neurons implies that primary Reelin action occurs at early/premigratory stages.

Full Abstract

Reelin signaling is essential for correct development of the mammalian brain. Reelin binds to apolipoprotein E receptor 2 and very low-density lipoprotein receptor and induces phosphorylation of Dab1. However, when and where these reactions occur is essentially unknown, and the primary function(s) of Reelin remain unclear. Here, we used alkaline phosphatase fusion of the receptor-binding region of Reelin to quantitatively investigate the localization of functional Reelin receptors (i.e., those on the plasma membrane as mature forms) in the developing brain. In the wild-type cerebral cortex, they are mainly present in the intermediate and subventricular zones, as well as in radial fibers, but much less in the cell bodies of the cortical plate. Functional Reelin receptors are much more abundant in the Reelin-deficient cortical plate, indicating that Reelin induces their downregulation and that it begins before the neurons migrate out of the intermediate zone. In the wild-type cerebellum, functional Reelin receptors are mainly present in the cerebellar ventricular zone but scarcely expressed by Purkinje cells that have migrated out of it. It is thus strongly suggested that Reelin exerts critical actions on migrating projection neurons at their early/premigratory stages en route to their final destinations, in the developing cerebral cortex and cerebellum.

Author information

Author/s: Uchida, Takayuki (T); Baba, Atsushi (A); Pérez-Martínez, F Javier (FJ); Hibi, Terumasa (T); Miyata, Takaki (T); Luque, Juan M (JM); Nakajima, Kazunori (K); Hattori, Mitsuharu (M);

Affiliation: Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Aug; vol 29 (issue 34) : pp 10653-62

Dates: Created 2009/08/27; Completed 2009/09/10;

PMID: 19710317, status: MEDLINE (last retrieval date: 9/10/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alkaline Phosphatase - metabolism
Animals
Animals, Newborn
Brain - cytology; embryology; growth & development
Calcium-Binding Protein, Vitamin D-Dependent - metabolism
Cell Adhesion Molecules, Neuronal - genetics; metabolism
Cell Movement - genetics; physiology
Cells, Cultured
Down-Regulation - genetics; physiology
Embryo, Mammalian
Extracellular Matrix Proteins - genetics; metabolism
Gene Expression Regulation, Developmental - physiology
Humans

LDL-Receptor Related Protein 1 - deficiency
LDL-Receptor Related Protein-Associated Protein - metabolism
Mice
Mice, Inbred ICR
Mice, Knockout
Mice, Neurologic Mutants
Microtubule-Associated Proteins - metabolism
Models, Biological
Nerve Tissue Proteins - genetics; metabolism
Neurons - physiology
Receptors, LDL - deficiency
Serine Endopeptidases - genetics; metabolism
Transfection

Associated Chemicals: Calcium-Binding Protein, Vitamin D-Dependent (0) ; Cell Adhesion Molecules, Neuronal (0) ; Dab1 protein, mouse (0) ; Extracellular Matrix Proteins (0) ; LDL-Receptor Related Protein 1 (0) ; LDL-Receptor Related Protein-Associated Protein (0) ; Microtubule-Associated Proteins (0) ; Mtap2 protein, mouse (0) ; Nerve Tissue Proteins (0) ; Receptors, LDL (0) ; VLDL receptor (0) ; calbindin (0) ; calretinin (0) ; Alkaline Phosphatase (EC 3.1.3.1) ; Serine Endopeptidases (EC 3.4.21.-) ; reelin protein (EC 3.4.21.-)

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