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在秀丽隐杆线虫发育过程中影响神经细胞谱系和细胞命运的突变。

Mutations that affect neural cell lineages and cell fates during the development of the nematode Caenorhabditis elegans.

作者信息

Horvitz H R, Sternberg P W, Greenwald I S, Fixsen W, Ellis H M

出版信息

Cold Spring Harb Symp Quant Biol. 1983;48 Pt 2:453-63. doi: 10.1101/sqb.1983.048.01.050.

Abstract

We have described 19 genes that affect neural cell lineages and cell fates during the development of C. elegans. These genes differ markedly in the nature, breadth, and specificity of their effects. Their only obvious common characteristic is that they all lack specificity for the nervous system, affecting both neural and nonneural development. For some of these genes (lin-5, lin-6, unc-59, unc-85), this nonspecificity probably reflects a general utilization of their products in cellular replication. In contrast, most of these genes appear to be highly specific in their effects, but their specificity is not on the basis of cell type but rather on the basis of some particular aspect of development. Specifically, unc-83 and unc-84 mutations affect certain precursor cells that generate both neural and nonneural descendants; lin-22 and lin-26 mutants lead to the generation of supernumerary neural cells with a concomitant loss of nonneural cells; lin-4, lin-14, lin-28, and lin-29 mutants perturb global aspects of developmental timing, altering the time of appearance (or preventing the appearance) of both neural and nonneural cells; lin-1, lin-8, lin-9, and lin-15 mutations affect the cell lineages of certain nonneuron -producing ectoblasts in hermaphrodites and of homologous neuron-producing ectoblasts in males; lin-12 mutations affect many sets of nonidentical homologs (cells of similar lineage history that express different fates), only some of which are neural; ced-3 mutations prevent all programmed cell deaths, again only some of which are neural. Of these 19 genes, only unc-86 is specific for neural as opposed to nonneural cell lineages. However, some unc-86 mutants are abnormal in chromosome segregation at meiosis, indicating that this gene also may affect nonneural aspects of development. One implication of these observations is that genes (and molecules) involved in neural development are likely to function in nonneural development as well. The genes lin-22, lin-12, unc-86, and ced-3 may play decision-making roles during C. elegans neurogenesis, as mutations in each of these genes cause specific transformations in the fates of particular cells. These genes and others like them may act within a hierarchy to effect decisions at different levels within cell lineages. For example, lin-22 animals display transformations affecting entire postembryonic cell lineages, unc-86 animals are altered at an intermediate level of certain cell lineages, and ced-3 animals are affected only in the ultimate fates of cells produced by terminal cell divisions.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

我们已经描述了19个在秀丽隐杆线虫发育过程中影响神经细胞谱系和细胞命运的基因。这些基因在其作用的性质、广度和特异性方面有显著差异。它们唯一明显的共同特征是对神经系统缺乏特异性,既影响神经发育也影响非神经发育。对于其中一些基因(lin-5、lin-6、unc-59、unc-85),这种非特异性可能反映了其产物在细胞复制中的普遍利用。相比之下,这些基因中的大多数在其作用上似乎具有高度特异性,但它们的特异性不是基于细胞类型,而是基于发育的某些特定方面。具体而言,unc-83和unc-84突变影响某些既能产生神经后代又能产生非神经后代的前体细胞;lin-22和lin-26突变体导致额外神经细胞的产生,同时非神经细胞减少;lin-4、lin-14、lin-28和lin-29突变体扰乱发育时间的全局方面,改变神经和非神经细胞出现的时间(或阻止其出现);lin-1、lin-8、lin-9和lin-15突变影响雌雄同体中某些不产生神经元的外胚层细胞谱系以及雄性中同源的产生神经元的外胚层细胞谱系;lin-12突变影响许多组不同的同源细胞(具有相似谱系历史但表达不同命运的细胞),其中只有一些是神经细胞;ced-3突变阻止所有程序性细胞死亡,同样只有一些是神经细胞死亡。在这19个基因中,只有unc-86对神经细胞谱系而非非神经细胞谱系具有特异性。然而,一些unc-86突变体在减数分裂时染色体分离异常,表明该基因也可能影响发育的非神经方面。这些观察结果的一个含义是,参与神经发育的基因(和分子)可能也在非神经发育中起作用。基因lin-22、lin-12、unc-86和ced-3可能在秀丽隐杆线虫神经发生过程中发挥决策作用,因为这些基因中的每一个发生突变都会导致特定细胞命运的特定转变。这些基因以及其他类似基因可能在一个层次结构中起作用,以在细胞谱系内的不同水平上影响决策。例如,lin-22突变动物表现出影响整个胚胎后细胞谱系的转变,unc-86突变动物在某些细胞谱系的中间水平发生改变,而ced-3突变动物仅在终末细胞分裂产生的细胞的最终命运上受到影响。(摘要截短至400字)

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