Effect of the weaver (wv) mutation on cerebellar neuron differentiation. II. Quantitation of neuron behavior in culture.
Effect of the weaver (wv) mutation on cerebellar neuron differentiation. II. Quantitation of neuron behavior in culture.
复制标题
韦弗（wv）突变对小脑神经元分化的影响。
DOI：
10.1016/0012-1606(85)90385-9
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发表时间：
1985
影响因子：
2.7
通讯作者：
D. Margolis
中科院分区：
文献类型：
--
作者：
M. Willinger;D. Margolis
对正常 (+/+)、杂合织布者 (+ wv) 和纯合织布者 (wv wv) 7 日龄小鼠小脑的分离培养物进行延时显微摄影，对神经元行为进行定量测量，以确定突变等位基因的剂量依赖性表达。颗粒细胞神经元神经突生长受损是剂量依赖性神经突回缩频率增加和生长锥前进速率降低的直接结果。对于+/+、+ wv 和wv wv 神经突，每个神经突的回缩次数分别为0.2、1.0 和2.0。对于+/+、+ wv 和 wv wv 颗粒细胞神经突，生长锥前进的最大速率分别为 1041、443 和 250 μm/天。在 wv wv 培养物中，神经突起始实际上有所增加，尽管神经突没有得到很好的维持。 +/+、+ wv 和 wv wv 神经元的神经突起始频率分别为 1.0、1.7 和 2.2。对体细胞位置振荡的测量表明，细胞中心在短时间内移动的距离与突变基因的数量成正比。核易位是体内和体外体细胞迁移的模式，在正常和突变培养物中以相同的频率和速率发生。 Weaver 基因表达诱导影响各种形态发生事件的细胞病理学，而不是在颗粒细胞分化的特定阶段产生块。据推测，细胞运动的剂量依赖性损伤反映了 weaver 基因在细胞表面或细胞骨架上的作用。
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.