A theoretical and experimental examination of cell lineage relationships among cerebellar Purkinje cells in the mouse.
A theoretical and experimental examination of cell lineage relationships among cerebellar Purkinje cells in the mouse.
复制标题
小鼠小脑浦肯野细胞之间细胞谱系关系的理论和实验研究。
DOI：
10.1006/dbio.1993.1058
复制
发表时间：
1993
影响因子：
2.7
通讯作者：
Herrup,K
中科院分区：
文献类型：
--
作者：
Vogel,MW;Herrup,K
在这篇论文中，我们继续研究细胞谱系在小鼠小脑浦肯野细胞群体发育中的作用。对蒲肯野细胞谱系的分析是基于+/LC↔野生型嵌合体中野生型蒲肯野细胞的计数。+/LcPurkinje细胞在出生后发育早期经历细胞自主退化，在嵌合动物中留下数量不等的野生型Purkinje细胞。利用理论、统计和实验方法，我们测试了各种发育模型，以解释+/LC↔野生型嵌合体中浦肯野细胞数量的数量发展。我们分析了基于细胞谱系与浦肯野细胞发育无关的假设以及我们之前的假设，即浦肯野细胞是在神经发生的早期阶段选择的少数前体细胞的后代。该理论方法基于神经元发育的克隆和非克隆假设，计算了假想的+/LC↔野生型嵌合体和近交系小鼠中浦肯野细胞的数量分布。将该模型的变异与已发表的+/LC↔C3H/HeJ、+/LC↔C57BL/6J、+/LC↔AKR/J嵌合体以及C3H/HeJ近交系小鼠的细胞计数进行了比较。统计方法通过蒙特卡罗模拟技术来评估观测数据与模型的不同变化的拟合的重要性。比较的结果表明，我们观察到的数据更有可能被克隆发育模型解释，而不是细胞谱系扮演次要角色的替代模型。我们的实验方法描述了一种新的+/LC↔C3H/HeJ嵌合体，在该嵌合体中，所有的浦肯野细胞(>；7900)都位于大脑的一侧。我们已经根据浦肯野细胞发育的克隆和非克隆模型分析了这个嵌合体。浦肯野细胞的极端不对称分布为存在少量产生浦肯野细胞的祖细胞的假设提供了额外的支持。我们的发现得出的结论是，虽然不能完全排除哺乳动物中枢神经系统发育的所有替代模式，但早期祖细胞假说是浦肯野细胞最可能的发育模式。
In this paper, we continue our examination of the role of cell lineage in the development of the cerebellar Purkinje cell population of the mouse. The analysis of Purkinje cell lineage is based on counts of the number of wild-type Purkinje cells in +/Lc↔ wild-type chimeras. +/LcPurkinje cells undergo a cell autonomous degeneration early in post-natal development leaving variable numbers of wild-type Purkinje cells in chimeric animals. Using theoretical, statistical, and experimental approaches, we have tested various developmental models to account for the numerical development of Purkinje cell numbers in the +/Lc↔ wild-type chimeras. We have analyzed models based on the assumption that cell lineages are irrelevant to Purkinje cell development, as well as our own previous hypothesis that Purkinje cells descend from a small number of progenitor cells selected during the early stages of neurogenesis. The theoretical approach calculates the distributions of Purkinje cell numbers in hypothetical +/Lc↔ wild-type chimeras and inbred mice based on both clonal and nonclonal hypotheses of neuronal development. Variations of the model are compared with published cell counts from +/Lc↔ C3H/HeJ, +/Lc↔ C57BL/6J, +/Lc↔ AKR/J chimeras, and C3H/HeJ inbred mice. The statistical approach assesses the significance of the fits of the observed data with different variations of the model by Monte Carlo simulation techniques. The results of the comparison suggest that our observed data is more likely to be explained by a clonal model of development than by alternate models in which cell lineages play a minor role. Our experimental approach describes a new +/Lc↔ C3H/HeJ chimera in which all of the Purkinje cells (>7900) are found on one side of the brain. We have analyzed this chimera with respect to clonal and nonclonal models of Purkinje cell development. The extreme asymmetric distribution of Purkinje cells provides added support to the hypothesis that there is a small number of progenitor cells that generate Purkinje cells. Our findings lead to the conclusion that while not all alternate models of mammalian CNS development can be completely excluded, the early progenitor hypothesis is the most probable model of Purkinje cell development.