title: ApoER2 and VLDLr are required for mediating reelin signalling pathway for normal migration and positioning of mesencephalic dopaminergic neurons.
abstract: The migration of mesencephalic dopaminergic (mDA) neurons from the subventricular zone to their final positions in the substantia nigra compacta (SNc), ventral tegmental area (VTA), and retrorubral field (RRF) is controlled by signalling from neurotrophic factors, cell adhesion molecules (CAMs) and extracellular matrix molecules (ECM). Reelin and the cytoplasmic adaptor protein Disabled-1 (Dab1) have been shown to play important roles in the migration and positioning of mDA neurons. Mice lacking Reelin and Dab1 both display phenotypes characterised by the failure of nigral mDA neurons to migrate properly. ApoER2 and VLDLr are receptors for Reelin signalling and are therefore part of the same signal transduction pathway as Dab1. Here we describe the roles of ApoER2 and VLDLr in the proper migration and positioning of mDA neurons in mice. Our results demonstrate that VLDLr- and ApoER2-mutant mice have both a reduction in and abnormal positioning of mDA neurons. This phenotype was more pronounced in VLDLr-mutant mice. Moreover, we provide evidence that ApoER2/VLDLr double-knockout mice show a phenotype comparable with the phenotypes observed for Reelin- and Dab1- mutant mice. Taken together, our results demonstrate that the Reelin receptors ApoER2 and VLDLr play essential roles in Reelin-mediated migration and positioning of mDA neurons.
authors: Institute for Anatomy and Cell Biology, Department of Molecular Embryology, Albert-Ludwigs-Universität, Freiburg, Germany.
authors: Ahmed
authors: A
authors: Sharaf
authors: Hans H
authors: HH
authors: Bock
authors: Björn
authors: B
authors: Spittau
authors: Elisabeth
authors: E
authors: Bouché
authors: Kerstin
authors: K
authors: Krieglstein
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D004622:Embryo, Mammalian; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D026502:LDL-Receptor Related Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
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