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

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)