Close homologue of adhesion molecule L1 promotes survival of Purkinje and granule cells and granule cell migration during murine cerebellar development
Autor: | Nada Zecevic, Melitta Schachner, Andrey Irintchev, Janina Siering, Shengming Yin, Laura Hoelters, Nicole Karl, Gunnar Hargus, Igor Jakovcevski, Nevena Djogo |
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Rok vydání: | 2009 |
Předmět: |
Male
Cerebellum Purkinje cell Cell Count Biology Polymerase Chain Reaction Mice Purkinje Cells 03 medical and health sciences 0302 clinical medicine Cell Movement Interneurons Pregnancy Precursor cell medicine Animals Cells Cultured 030304 developmental biology Mice Knockout Neurons 0303 health sciences Cell Death Cell growth Cell adhesion molecule General Neuroscience Cell Differentiation Cell migration Dendrites Embryo Mammalian Granule cell Immunohistochemistry Cell biology Mice Inbred C57BL CXCL3 medicine.anatomical_structure Animals Newborn nervous system Female Cell Adhesion Molecules Neuroglia 030217 neurology & neurosurgery |
Zdroj: | The Journal of Comparative Neurology. 513:496-510 |
ISSN: | 1096-9861 0021-9967 |
DOI: | 10.1002/cne.21981 |
Popis: | Several L1-related adhesion molecules, expressed in a well-coordinated temporospatial pattern during development, are important for fine tuning of specific cerebellar circuitries. We tested the hypothesis that CHL1, the close homologue of L1, abundantly expressed in the developing and adult cerebellum, is also required for normal cerebellar histogenesis. We found that constitutive ablation of CHL1 in mice caused significant loss (20–23%) of Purkinje and granule cells in the mature 2-month-old cerebellum. The ratio of stellate/basket interneurons to Purkinje cells was abnormally high (+38%) in CHL1-deficient (CHL1−/−) mice compared with wild-type (CHL1+/+) littermates, but the γ-aminobutyric acid (GABA)ergic synaptic inputs to Purkinje cell bodies and dendrites were normal, as were numbers of Golgi interneurons, microglia, astrocytes, and Bergmann glia. Purkinje cell loss occurred before the first postnatal week and was associated with enhanced apoptosis, presumably as a consequence of CHL1 deficiency in afferent axons. In contrast, generation of granule cells, as indicated by in vivo analyses of cell proliferation and death, was unaffected in 1-week-old CHL1−/− mice, but numbers of migrating granule cells in the molecular layer were increased. This increase was likely related to retarded cell migration because CHL1−/− granule cells migrated more slowly than CHL1+/+ cells in vitro, and Bergmann glial processes guiding migration in vivo expressed CHL1 in wild-type mice. Granule cell deficiency in adult CHL1−/− mice appeared to result from decreased precursor cell proliferation after the first postnatal week. Our results indicate that CHL1 promotes Purkinje and granule cell survival and granule cell migration during cerebellar development. J. Comp. Neurol. 513:496–510, 2009. © 2009 Wiley-Liss, Inc. |
Databáze: | OpenAIRE |
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