Molecular plasticity of adult Bergmann fibers is associated with radial migration of grafted Purkinje cells.
Embryonic Purkinje cells (PCs) from cerebellar primordia grafted in adult pcd mutant cerebellum replace missing PCs of the host, and become synaptically integrated into the defective cerebellar circuit. This process of neuronal replacement starts with the invasion of grafted PCs into the host cerebellum, and their radial migration through its molecular layer. The present study is aimed at determining whether the glial axes for this migration are embryonic radial glial cells that comigrate with the grafted PCs, or adult Bergmann fibers of the host, transiently reexpressing the molecular cues needed for their guidance of the migration. Transplants from a transgenic mouse line (Krox-20/lacZ14) in which Bergmann fibers could be identified by lacZ expression reveal that, despite the presence of X-gal-stained Bergmann fibers in the graft remnants and of grafted PCs in the host molecular layer, all Bergmann fibers in the host cerebellum lack of beta-galactosidase activity. Thus, these migratory axes belong to the host, not to the donor. Transplants from normal isogenic mouse embryos show that during the radial migration of grafted PCs (7 d after grafting) the involved host Bergmann fibers reexpress nestin (identified with monoclonal antibody Rat-401 immunostaining), normally expressed only by immature Bergmann fibers. Five days later, when grafted PCs have arrested their migration, host Bergmann fibers again become Rat-401 negative. These results indicate that embryonic PCs can trigger in adult cerebellum the molecular changes necessary for their own migration and ultimate synaptic integration in the host cortical circuitry.
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INSERM U. 106, Hôpital de la Salpétrière, Paris, France.
Alvarado-Mallart
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Frain
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Vernet
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D000818:Animals; D000911:Antibodies, Monoclonal; D002465:Cell Movement / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000196:embryology*; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D016332:Fetal Tissue Transplantation; D015870:Gene Expression; D007381:Intermediate Filament Proteins / Q000378:metabolism; D007763:Lac Operon; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000378:metabolism; D009419:Nerve Tissue Proteins; D064231:Nestin; D011689:Purkinje Cells / Q000502:physiology / Q000637:transplantation*; D014157:Transcription Factors; D001616:beta-Galactosidase / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D014157:Transcription Factors; D001616:beta-Galactosidase