Divergent roles of ApoER2 and Vldlr in the migration of cortical neurons.
Reelin, its lipoprotein receptors [very low density lipoprotein receptor (Vldlr) and apolipoprotein E receptor 2 (ApoER2; also known as Lrp8)], and the cytoplasmic adaptor protein disabled 1 (Dab1) are important for the correct formation of layers in the cerebral cortex. Reeler mice lacking the reelin protein show altered radial neuronal migration resulting in an inversion of cortical layers. ApoER2 Vldlr double-knockout mutants and Dab1 mutants show a reeler-like phenotype, whereas milder phenotypes are found if only one of the two lipoprotein receptors for reelin is absent. However, the precise role of the individual reelin receptors in neuronal migration remained unclear. In the study reported here, we performed fate mapping of newly generated cortical neurons in single and double receptor mutants using bromodeoxyuridine-labeling and layer-specific markers. We present evidence for divergent roles of the two reelin receptors Vldlr and ApoER2, with Vldlr mediating a stop signal for migrating neurons and ApoER2 being essential for the migration of late generated neocortical neurons.
Hack
Iris
I
Institut für Anatomie und Zellbiologie, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany.
Hellwig
Sabine
S
Junghans
Dirk
D
Brunne
Bianka
B
Bock
Hans H
HH
Zhao
Shanting
S
Frotscher
Michael
M
D000818:Animals; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D026502:LDL-Receptor Related Proteins; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000091042:Reelin Protein; D012097:Repressor Proteins / Q000378:metabolism; D020825:T-Box Domain Proteins; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D026502:LDL-Receptor Related Proteins; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; C492271:Tbr1 protein, mouse; C434949:Tle4 protein, mouse; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717128:Reln protein, mouse