Chalfie M, Horvitz H R, Sulston J E
Cell. 1981 Apr;24(1):59-69. doi: 10.1016/0092-8674(81)90501-8.
Cells in the nematode Caenorhabditis elegans arise from invariant cell lineages. Mutations in two genes, unc-86 and lin-4, alter multiple and mutually exclusive sets of these lineages. In these mutants, particular cells repeat division patterns normally associated with their parental or grandparental progenitors. The effects of unc-86 are highly specific, altering in equivalent ways the lineages of three post-embryonic neuroblasts that in the wild-type undergo similar division patterns. The effects of lin-4 are more varied, resulting in a number of types of lineage reiterations as well as in supernumerary molts and the continued synthesis of larval-specific cuticle. The reiteration of a given cell division or pattern of cell divisions leads to the repeated generation of cells indistinguishable (by both light and electron microscopy) from those produced after the same division or pattern of cell divisions in the wild-type. This correlation between lineage history and cell fate suggests that in C. elegans a particular sequence of cell divisions may be necessary for the generation of a particular cell type. Reiterative lineages, often referred to as stem cell lineages, may be basic to the development of nematodes and other organisms. We suggest that the wild-type unc-86 and lin-4 genes act to modify latent reiterative cell lineages, which are revealed when the activity of one of these genes is eliminated.
线虫秀丽隐杆线虫中的细胞起源于不变的细胞谱系。unc-86和lin-4这两个基因的突变会改变这些谱系中的多个且相互排斥的细胞组。在这些突变体中，特定细胞会重复通常与其亲代或祖代祖细胞相关的分裂模式。unc-86的作用具有高度特异性，以等效方式改变了三个胚胎后神经母细胞的谱系，这些神经母细胞在野生型中经历相似的分裂模式。lin-4的作用则更为多样，导致多种类型的谱系重复，以及额外的蜕皮和幼虫特异性表皮的持续合成。给定细胞分裂或细胞分裂模式的重复会导致产生与野生型相同分裂或细胞分裂模式后产生的细胞无法区分（通过光学和电子显微镜）的细胞。这种谱系历史与细胞命运之间的相关性表明，在秀丽隐杆线虫中，特定的细胞分裂序列可能是产生特定细胞类型所必需的。重复谱系，通常称为干细胞谱系，可能是线虫和其他生物发育的基础。我们认为野生型unc-86和lin-4基因的作用是修饰潜在的重复细胞谱系，当其中一个基因的活性被消除时，这些谱系就会显现出来。
