Moving up or moving down? Malpositioned cerebellar unipolar brush cells in reeler mouse.
Cerebellar morphogenesis occurs through a complex interplay of cell proliferation and migration that in mouse and rat begins about midgestation and ends in the third postnatal week. Cerebellar cells derive from germinative matrices in the ventricular zone and the external granular layer. Like granule cells, unipolar brush cells (UBCs) are excitatory interneurons situated in the granular layer of the cortex and innervated by mossy fibers. While granule cells are produced from the external granular layer, the generation of UBCs is still controversial. We utilized the reeler mutant mouse, which has widespread misplacement of neurons due to lack of Reelin protein, to ascertain the origin of UBCs. In the reeler cerebellum, which is small and lacks foliation, Purkinje cells are greatly reduced in number and in large part are located ectopically in deep cerebellar masses. Granule cells are also reduced in number and form an irregular granule cell layer. In this study we demonstrate that the reeler mutation influences the positioning of UBCs and also significantly reduces their number. Both subsets of UBCs identified in normal mouse, the calretinin-positive and the metabotropic glutamate receptor 1alpha-positive subsets, are affected in the reeler. About 40% of the calretinin-positive UBCs are ectopically situated in the deep cerebellar regions and the immediate vicinity of the ependyma of the fourth ventricle. Ectopic UBCs have discrete, although somewhat looser brushes than granular layer UBCs, but form synaptic junctions with complex axon terminals, possibly belonging to mossy fibers and UBC axons, like their normally situated counterpart. The observed displacement of UBCs in the reeler suggests that they originate from the ventricular zone.
Ilijic
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Northwestern University Institute for Neuroscience, Searle 5-470, 320 East Superior Street, Chicago, IL 60611, USA.
Guidotti
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Mugnaini
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D000818:Animals; D001931:Brain Mapping; D064032:Calbindin 2; D002452:Cell Count / Q000379:methods; D002531:Cerebellum / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D007395:Interneurons / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000033:anatomy & histology*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D000091042:Reelin Protein; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013238:Stereotaxic Techniques; D016708:Synaptophysin / Q000378:metabolism
C576511:Calb2 protein, mouse; C576512:Calb2 protein, rat; D064032:Calbindin 2; D000091042:Reelin Protein; C000717129:Reln protein, rat; D064030:S100 Calcium Binding Protein G; D016708:Synaptophysin; C000717128:Reln protein, mouse