Figure 2 - uploaded by Chris I De Zeeuw
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Granule cells populate the molecular layer in Bicd2−/− cerebellar cortex. (a,b) Sagittal sections of P11 and P16 cerebellum stained with H&E. The low magnification in a illustrates the intact folial organization of the vermis of Bicd2−/− cerebellar cortex. The high magnification in b shows the absence of the internal granule cell layer (igl) and a high density of cells in the molecular layer (ml) in Bicd2−/− cerebellum. (c) Sagittal sections of P16 cerebellum immunostained with anti-NeuN and anti-calbindin. Note that in Bicd2−/− cerebellar cortex the Purkinje cell layer (Pcl, calbindin+ cells) is localized adjacent to the white matter (wm), and that Purkinje cell dendritic arbors extend up to the pial surface. (d–g) Double-labelling confocal immunofluorescence of α6 GABAA receptor subunit (α6GABAAR) with parvalbumine (Parv) and VGluT1, respectively, in transverse sections of P20 cerebellum. Note the presence of many α6GABAAR+ cells (arrow head in e), a moderate amount of Parv+ cells (arrow in e), and abundant VGluT1 labelling (g) in the ml/gl layer of Bicd2−/− cerebellar cortex. The arrow in f points to a glomerulus containing both α6GABAAR+ granule cell dendritic processes and a VGluT1+ mossy fibre ending. Occasionally, double-labelled glomeruli-like structures occur near the Pcl of Bicd2−/− cerebellar cortex (arrow in g). Optical sections in d–g, 1 μm. Scale bars: 200 μm (a), 25 μm (b,d), 50 μm (c).
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Bicaudal-D (BICD) belongs to an evolutionary conserved family of dynein adaptor proteins. It was first described in Drosophila as an essential factor in fly oogenesis and embryogenesis. Missense mutations in a human BICD homologue, BICD2, have been linked to a dominant mild early onset form of spinal muscular atrophy. Here we further examine the in...
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... of Bicd2 À / À mice at P15-P25 revealed no gross alterations in internal organs, except for a smaller size, and confirmed that Bicd2 À / À mice developed severe hydrocephalus, which was characterized by progressive expansion of lateral ventricles (ventriculomegaly), loss of white matter and ependymal cells surrounding the ventricles, severe thinning of the cortex and atrophy of other telencephalic areas, including striatum, hippo- campus and septum ( Fig. 1d; Supplementary Fig. 2A-D). Apart from cerebellar cortex (see below), other brain regions and spinal cord appeared normal ( Supplementary Fig. 2F). Analysis of the aqueduct at P5 suggested a smaller diameter indicative of aqueductal stenosis (Supplementary Fig. 2E). ...
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... from cerebellar cortex (see below), other brain regions and spinal cord appeared normal ( Supplementary Fig. 2F). Analysis of the aqueduct at P5 suggested a smaller diameter indicative of aqueductal stenosis (Supplementary Fig. 2E). ...
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... internal granule cell layer (IGL) along radial processes of Bergmann glia. Granule and glial cells originate from different precursors 19,20 , which makes it easier to establish the origin of migration deficits. Bicd2 À / À mice showed a dis- proportionally small cerebellum with grossly intact subdivision in vermis and hemispheres and foliation ( Fig. 2a; Supplementary Fig. 2), but an altered laminar organization, indicative of the absence of radial granule cell migration. Instead of laminar subdivision into molecular, Purkinje cell and granular layer, in Bicd2 À / À cerebellar cortex the cell bodies of Purkinje cells (Calbindin þ , NeuN À ) were positioned near the white matter, while ...
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... and glial cells originate from different precursors 19,20 , which makes it easier to establish the origin of migration deficits. Bicd2 À / À mice showed a dis- proportionally small cerebellum with grossly intact subdivision in vermis and hemispheres and foliation ( Fig. 2a; Supplementary Fig. 2), but an altered laminar organization, indicative of the absence of radial granule cell migration. Instead of laminar subdivision into molecular, Purkinje cell and granular layer, in Bicd2 À / À cerebellar cortex the cell bodies of Purkinje cells (Calbindin þ , NeuN À ) were positioned near the white matter, while other neurons (NeuN þ ) were spread over a single superficial layer (Fig. 2b,c). ...
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... indicative of the absence of radial granule cell migration. Instead of laminar subdivision into molecular, Purkinje cell and granular layer, in Bicd2 À / À cerebellar cortex the cell bodies of Purkinje cells (Calbindin þ , NeuN À ) were positioned near the white matter, while other neurons (NeuN þ ) were spread over a single superficial layer (Fig. 2b,c). This layer contained both molecular layer interneurons (NeuN þ , Parvalbumin þ , Calbindin À ), as well as a high density of granule cells, identified by immunostaining for the a6 GABA A receptor subunit that is only expressed by adult, post-migratory granule cells (Fig. 2d-g). Cerebellar Golgi cells (mGluR2 þ ), which are localized ...
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... other neurons (NeuN þ ) were spread over a single superficial layer (Fig. 2b,c). This layer contained both molecular layer interneurons (NeuN þ , Parvalbumin þ , Calbindin À ), as well as a high density of granule cells, identified by immunostaining for the a6 GABA A receptor subunit that is only expressed by adult, post-migratory granule cells (Fig. 2d-g). Cerebellar Golgi cells (mGluR2 þ ), which are localized in the granule cell layer of wild-type mouse cerebellar cortex, were concentrated between the white matter and the Purkinje cell layer, and did not occur in Bicd2 À / À molecular/granule cell layer ( Supplementary Fig. 4). Staining for the glutamate synaptic ...
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... some populations of neuron vesicle transporter VGluT1, which is present in parallel fibre and mossy fibre endings in the cerebellar molecular and granular layers, respectively, revealed prominent punctate staining in the Bicd2 À / À molecular/granular layer, indicative of the presence of parallel fibre endings (Fig. 2f,g). VGluT1-immunostaining near the Purkinje cell layer also revealed sporadic larger irregular structures resembling mossy fibre endings, which accordingly co- distributed with a6 GABA A receptor immunoreactivity, indi- cative of granule cell dendritic processes in the glomeruli (Fig. 2g). Immunostaining for VGluT2, which is present in ...
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... layer, indicative of the presence of parallel fibre endings (Fig. 2f,g). VGluT1-immunostaining near the Purkinje cell layer also revealed sporadic larger irregular structures resembling mossy fibre endings, which accordingly co- distributed with a6 GABA A receptor immunoreactivity, indi- cative of granule cell dendritic processes in the glomeruli (Fig. 2g). Immunostaining for VGluT2, which is present in an additional and partially overlapping population of mossy fibre endings as well as in climbing fibre endings, confirmed the presence of a low number of mossy fibre endings and indicated impaired climbing fibre innervation of Purkinje cells in Bicd2 À / À cerebellar cortex ( ...
