Effect of the weaver (wv) mutation on cerebellar neuron differentiation. II. Quantitation of neuron behavior in culture |
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| Authors: | M Willinger D M Margolis |
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| Affiliation: | 1. Department of Neuropathology, Harvard Medical School and Children''s Hospital, Boston, Massachusetts 02115 USA;2. Department of Neuroscience, Harvard Medical School and Children''s Hospital, Boston, Massachusetts 02115 USA;1. CEFAGE-UE and Department of Management, University of Évora, Palácio do Vimioso (Gab. 224), Largo Marquês de Marialva, 8, 7000-809 Évora, Portugal;2. Asia Center, Harvard University, Cambridge, MA 02138, USA;3. Ryerson University, Toronto, ON M5B 2K3, Canada;1. Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA;2. Department of Psychology and Neuroscience, Dalhousie University, 1355 Oxford Street, Halifax, NS B3H 4R2, Canada;1. University of Lyon, UJML3, iaelyon School of Management, Magellan, 1C, avenue des Frères Lumière - CS 78242 - 69372 LYON CEDEX 08, France;2. University of Lille, ULR 4112 – LSMRC, F-5900 Lille, France;1. Free University of Bozen/Bolzano, Universitätsplatz 1, I-39100 Bolzano, Italy;2. Otto-von-Guericke University Magdeburg, Universitätsplatz 2, D-39106 Magdeburg, Germany;3. University of North Carolina at Greensboro, 349 Bryan Building, P.O. Box 26170, Greensboro, NC 27402-6165, USA |
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| Abstract: | Quantitative measurements of neuron behavior from time-lapse microcinematography of dissociated cultures of normal (+/+), heterozygous weaver (+/wv), and homozygous weaver (wv/wv) 7-day-old mouse cerebellum were performed to identify dose-dependent expressions of the mutant allele. Impaired neurite growth by granule cell neurons is a direct result of a dose-dependent increased frequency of neurite retraction and decreased rate of growth cone advancement. The number of retractions per neurite is 0.2, 1.0, and 2.0 for +/+, +/wv, and wv/wv neurites, respectively. Maximal rates of growth cone advancement are 1041, 443, and 250 micron/day for +/+, +/wv, and wv/wv granule cell neurites, respectively. Neurite initiation is actually increased in wv/wv cultures, though the neurites are not well sustained. The frequency of neurite initiation is 1.0, 1.7, and 2.2 for +/+, +/wv, and wv/wv neurons, respectively. Measurements of oscillations of somal position revealed that the cell center moves increasing distances over short times in proportion to the number of mutant genes. Nuclear translocation, the mode of somal migration in vivo and in vitro, occurs at the same frequency and rate in normal and mutant cultures. Weaver gene expression induces a cytopathology affecting various morphogenetic events rather than producing a block at a specific stage in granule cell differentiation. It is hypothesized that the dose-dependent impairments of cell motility reflect weaver gene action at the cell surface or cytoskeleton. |
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