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Granule Cells and Cerebellar Boundaries: Analysis ofUnc5h3Mutant Chimeras
- Source :
- The Journal of Neuroscience. 20:4129-4137
- Publication Year :
- 2000
- Publisher :
- Society for Neuroscience, 2000.
-
Abstract
- Mutations in theUnc5h3gene, a receptor for the netrin 1 ligand, result in abnormal migrations of both Purkinje and granule cells to regions outside the cerebellum and of granule cells to regions within the cerebellum. Because both Purkinje and granule cells express this molecule, we sought to determine whether one or both of these cell types are the primary target of the mutation.Chimeric mice were made between wild-type ROSA26 transgenic mouse embryos (whose cells express β-galactosidase) andUnc5h3mutant embryos. The resulting chimeric brains exhibited a range of phenotypes. Chimeras that had a limited expression of the extracerebellar phenotype (movement of cerebellar cells into the colliculus and midbrain tegmentum) and the intracerebellar phenotype (migration of granule cells into white matter) had a normal-appearing cerebellum, whereas chimeras that had more ectopic cells had attenuated anterior cerebellar lobules. Furthermore, the colonization of colliculus and midbrain tegmentum by cerebellar cells was not equivalent in all chimeras, suggesting different origins for extracerebellar ectopias in these regions.The granule cells of the extracerebellar ectopias were almost entirely derived fromUnc5h3/Unc5h3mutant embryos, whereas the ectopic Purkinje cells were a mixture of both mutant and wild-type cells. Intracerebellar ectopias in the chimera were composed exclusively of mutant granule cells. These findings demonstrate that both inside and outside the cerebellum, the granule cell is the key cell type to demarcate the boundaries of the cerebellum.
- Subjects :
- Cell type
Cerebellum
Genotype
Recombinant Fusion Proteins
Mitosis
Mice, Inbred Strains
Receptors, Cell Surface
Biology
Cytoplasmic Granules
Ligands
Mice
Purkinje Cells
Chimera (genetics)
Cell Movement
Netrin
medicine
Animals
ARTICLE
Coloring Agents
Neurons
General Neuroscience
Granule cell
Immunohistochemistry
Cell biology
Phenotype
medicine.anatomical_structure
nervous system
Mutation
Neuroglia
Midbrain tegmentum
Netrin Receptors
Neuroscience
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....d3817bfdc3ffc7e4ab12df081a62385f