Reelin is essential for neuronal migration but not for radial glial elongation in neonatal ferret cortex.
Numerous functions related to neuronal migration are linked to the glycoprotein reelin. Reelin also elongates radial glia, which are disrupted in mutant reeler mice. Our lab developed a model of cortical dysplasia in ferrets that shares features with the reeler mouse, including impaired migration of neurons into the cerebral cortex and disrupted radial glia. Explants of normal ferret cortex in coculture with dysplastic ferret cortex restore the deficits in this model. To determine if reelin is integral to the repair, we used explants of P0 mouse cortex either of the wild type (WT) or heterozygous (het) for the reelin gene, as well as P0 reeler cortex (not containing reelin), in coculture with organotypic cultures of dysplastic ferret cortex. This arrangement revealed that all types of mouse cortical explants (WT, het, reeler) elongated radial glia in ferret cortical dysplasia, indicating that reelin is not required for proper radial glial morphology. Migration of cells into ferret neocortex, however, did not improve with explants of reeler cortex, but was almost normal after pairing with WT or het explants. We also placed an exogenous source of reelin in ferret cultures at the pial surface to reveal that migrating cells move toward the reelin source in dysplastic cortex; radial glia in these cultures were also improved toward normal. Our results demonstrate that the normotopic position of reelin is important for proper neuronal positioning, and that reelin is capable of elongating radial glial cells but is not the only radialization factor.
Schaefer
Alisa
A
USUHS, Bethesda, Maryland 20814, USA.
Poluch
Sylvie
S
Juliano
Sharon
S
D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites; D050256:Antimitotic Agents / Q000494:pharmacology; D001973:Bromodeoxyuridine; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D048429:Cell Size; D002540:Cerebral Cortex / Q000166:cytology* / Q000502:physiology*; D018920:Coculture Techniques; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D005289:Ferrets / Q000502:physiology*; D005456:Fluorescent Dyes; D005838:Genotype; D006801:Humans; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D011247:Pregnancy; D000091042:Reelin Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*
D000963:Antimetabolites; D050256:Antimitotic Agents; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D008746:Methylazoxymethanol Acetate; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D001973:Bromodeoxyuridine; C030667:methylazoxymethanol