Close homologue of adhesion molecule L1 promotes survival of Purkinje and granule cells and granule cell migration during murine cerebellar development.
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Close homologue of adhesion molecule L1 promotes survival of Purkinje and granule cells and granule cell migration during murine cerebellar development. / Jakovcevski, Igor; Siering, Janina; Hargus, Gunnar; Karl, Nicole; Hoelters, Laura Sophie; Djogo, Nevena; Yin, Shengming; Zecevic, Nada; Schachner, Melitta; Irintchev, Andrey.
in: J COMP NEUROL, Jahrgang 513, Nr. 5, 5, 2009, S. 496-510.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Close homologue of adhesion molecule L1 promotes survival of Purkinje and granule cells and granule cell migration during murine cerebellar development.
AU - Jakovcevski, Igor
AU - Siering, Janina
AU - Hargus, Gunnar
AU - Karl, Nicole
AU - Hoelters, Laura Sophie
AU - Djogo, Nevena
AU - Yin, Shengming
AU - Zecevic, Nada
AU - Schachner, Melitta
AU - Irintchev, Andrey
PY - 2009
Y1 - 2009
N2 - 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 gamma-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.
AB - 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 gamma-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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 513
SP - 496
EP - 510
JO - J COMP NEUROL
JF - J COMP NEUROL
SN - 0021-9967
IS - 5
M1 - 5
ER -