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

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) o...

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Bibliographic Details
Published in:The Journal of neuroscience 2009-08, Vol.29 (34), p.10653-10662
Main Authors: Uchida, Takayuki, Baba, Atsushi, Pérez-Martínez, F Javier, Hibi, Terumasa, Miyata, Takaki, Luque, Juan M, Nakajima, Kazunori, Hattori, Mitsuharu
Format: Article
Language:English
Subjects:
Alkaline Phosphatase - metabolism
Animals
Animals, Newborn
Brain - cytology
Brain - embryology
Brain - growth & development
Calbindin 2
Calbindins
Cell Adhesion Molecules, Neuronal - genetics
Cell Adhesion Molecules, Neuronal - metabolism
Cell Movement - genetics
Cell Movement - physiology
Cells, Cultured
Down-Regulation - genetics
Down-Regulation - physiology
Embryo, Mammalian
Extracellular Matrix Proteins - genetics
Extracellular Matrix Proteins - metabolism
Gene Expression Regulation, Developmental - physiology
Humans
LDL-Receptor Related Protein-Associated Protein - metabolism
Low Density Lipoprotein Receptor-Related Protein-1 - deficiency
Mice
Mice, Inbred ICR
Mice, Knockout
Mice, Neurologic Mutants
Microtubule-Associated Proteins - metabolism
Models, Biological
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurons - physiology
Receptors, LDL - deficiency
S100 Calcium Binding Protein G - metabolism
Serine Endopeptidases - genetics
Serine Endopeptidases - metabolism
Transfection
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Summary: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.
ISSN:1529-2401
DOI:10.1523/JNEUROSCI.0345-09.2009