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) 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.
Uchida
Takayuki
T
Department of Biomedical Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Baba
Atsushi
A
Pérez-Martínez
F Javier
FJ
Hibi
Terumasa
T
Miyata
Takaki
T
Luque
Juan M
JM
Nakajima
Kazunori
K
Hattori
Mitsuharu
M
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D064032:Calbindin 2; D064026:Calbindins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D026563:LDL-Receptor Related Protein-Associated Protein / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000172:deficiency; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D011973:Receptors, LDL / Q000172:deficiency; D000091042:Reelin Protein; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D064032:Calbindin 2; D064026:Calbindins; D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D026563:LDL-Receptor Related Protein-Associated Protein; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D000091042:Reelin Protein; D064030:S100 Calcium Binding Protein G; C036053:VLDL receptor; D000469:Alkaline Phosphatase; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases