Rescue of the reeler phenotype in the dentate gyrus by wild-type coculture is mediated by lipoprotein receptors for Reelin and Disabled 1.
Reelin is a positional signal for the lamination of the dentate gyrus. In the reeler mutant lacking Reelin, granule cells are scattered all over the dentate gyrus. We have recently shown that the reeler phenotype of the dentate gyrus can be rescued in vitro by coculturing reeler hippocampal slices with slices from wild-type hippocampus. Here we studied whether Reelin from other brain regions can similarly induce this rescue effect and whether it is mediated via the Reelin receptors apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDLR). We found that coculturing reeler hippocampal slices with slices from wild-type olfactory bulb, cerebellum, and neocortex rescued the reeler phenotype as seen before with hippocampal slices, provided that the Reelin-synthesizing cells of these regions were placed near the marginal zone of the reeler hippocampal slice. However, coculturing wild-type hippocampal slices with hippocampal slices from mutants deficient in ApoER2 and VLDLR did not rescue the reeler-like phenotype in these cultures. Similarly, no rescue of the reeler-like phenotype was observed in slices from mutants lacking Disabled 1 (Dab1), an adapter protein downstream of Reelin receptors. Conversely, reeler hippocampal slices were rescued by coculturing them with slices from Dab1(-/-) mutants or ApoER2(-/-)/VLDLR(-/-) mice. These findings show that Reelin from other brain regions can substitute for the loss of hippocampal Reelin and that rescue of the reeler phenotype observed in our coculture studies is mediated via lipoprotein receptors for Reelin and Dab1.
Zhao
Shanting
S
Institut für Anatomie und Zellbiologie, Albert-Ludwigs-Universität Freiburg, D-79104 Freiburg, Germany.
Chai
Xuejun
X
Bock
Hans H
HH
Brunne
Bianka
B
Förster
Eckart
E
Frotscher
Michael
M
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D018920:Coculture Techniques; D018891:Dentate Gyrus / Q000002:abnormalities* / Q000166:cytology; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D026502:LDL-Receptor Related Proteins; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009421:Nervous System Malformations / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D009924:Organ Culture Techniques; D010641:Phenotype; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics*; D018110:Receptors, Lipoprotein / Q000235:genetics*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism
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; D018110:Receptors, Lipoprotein; D000091042:Reelin Protein; C000717129:Reln protein, rat; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases