Rescue of ataxia and preplate splitting by ectopic expression of Reelin in reeler mice.
The gene mutated in reeler (reelin) encodes a protein secreted by neurons in the developing brain that controls laminar positioning of migrating cells in the CNS by an unknown mechanism. To investigate Reelin function, we used the nestin promoter to express Reelin ectopically in the ventricular zone and other brain regions in transgenic mice. In the presence of the endogenous protein, ectopic Reelin did not alter cell migration in the neocortex or the cerebellum. However, in the reeler background, ectopic Reelin induced tyrosine phosphorylation of Dab-1 in the ventricular zone and rescued some, but not all, of the neuroanatomic and behavioral abnormalities characteristic of reeler. These results indicate that Reelin does not function simply as a positional signal. Rather, it appears to participate in multiple events critical for neuronal migration and cell positioning.
Magdaleno
Susan
S
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105, USA.
Keshvara
Lakhu
L
Curran
Tom
T
D000818:Animals; D001259:Ataxia / Q000235:genetics* / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics*; D001921:Brain / Q000002:abnormalities* / Q000166:cytology / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency* / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D002828:Choristoma / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000002:abnormalities* / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins; D009421:Nervous System Malformations / Q000235:genetics* / Q000378:metabolism; D064231:Nestin; D011401:Promoter Regions, Genetic / Q000235:genetics; D000091042:Reelin Protein; D012697:Serine Endopeptidases
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D000091042:Reelin Protein; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases