Effect of the weaver ( wv) mutation on cerebellar neuron differentiation : II. Quantitation of neuron behavior in culture

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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 μm/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.