A cell that dies during wild-type C. elegans development can function as a neuron in a ced-3 mutant.

Mutations in the C. elegans gene ced-3 prevent almost all programmed cell deaths, so that in a ced-3 mutant there are many extra cells. We show that the pharyngeal neuron M4 is essential for feeding in wild-type worms, but in a ced-3 mutant, one of the extra cells, probably MSpaaaaap (the sister of M4), can sometimes take over M4's function.

The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events.

The lin-14 locus of Caenorhabditis elegans plays an important role in specifying the normal timing and sequence of developmental events in the lateral hypodermal cell lineages. The results of gene dosage, complementation, and temperature-shift experiments indicate that the fates expressed by cells at successive stages of these cell lineages are specified by the level of lin-14 activity and that lin-14 acts at multiple times during development to control stage-specific choices of cell fate. Our observations suggest that during normal development a reduction in the level of lin-14 gene function causes the sequential expression of stage-specific cell fates.

A genetic pathway for the specification of the vulval cell lineages of Caenorhabditis elegans.

Twenty-three genes have been assigned to particular steps in a genetic pathway for the specification of the vulval cell lineages of the nematode Caenorhabditis elegans. Mutations in most of these genes cause homoeotic transformations in the fates of individual cells, suggesting that these lineages may be specified by a series of decisions that distinguish between alternative cell fates. Fifteen of the genes function in a system involved in the intracellular response to the extracellular signal that induces vulval formation.

C. elegans unc-105 mutations affect muscle and are suppressed by other mutations that affect muscle.

Certain mutations in the unc-105 II gene of the nematode Caenorhabditis elegans have dominant effects on morphology and behavior: animals become small, severely hypercontracted and paralyzed. These unc-105 mutants revert both spontaneously and with mutagens at high frequencies to a wild-type phenotype. Most of the reversion events are intragenic, apparently because the null (loss-of-function) phenotype of unc-105 is wild type.

Mutations with dominant effects on the behavior and morphology of the nematode Caenorhabditis elegans.

We have analyzed 31 mutations that have dominant effects on the behavior or morphology of the nematode Caenorhabditis elegans. These mutations appear to define 15 genes. We have studied ten of these genes in some detail and have been led to two notable conclusions.

A visible allele of the muscle gene sup-10X of C. elegans.

In this paper, we extend our previous analyses of a set of genes in Caenorhabditis elegans that are involved in muscle structure and function: unc-93 III, sup-9 II, sup-10 X and sup-11 I. We describe an unusual, visible allele of sup-10, examine how this allele interacts genetically with mutations in other genes of this set and propose that the wild-type products of the unc-93 and sup-10 loci may be components of a protein complex. We also describe a new gene of this set, sup-18 III, and the interaction of sup-18 alleles with mutations in the other genes.

Genetic control of programmed cell death in the nematode C. elegans.

The wild-type functions of the genes ced-3 and ced-4 are required for the initiation of programmed cell deaths in the nematode Caenorhabditis elegans. The reduction or loss of ced-3 or ced-4 function results in a transformation in the fates of cells that normally die; in ced-3 or ced-4 mutants, such cells instead survive and differentiate, adopting fates that in the wild type and associated with other cells. ced-3 and ced-4 mutants appear grossly normal in morphology and behavior, indicating that programmed cell death is not an essential aspect of nematode development.

Pattern formation during vulval development in C. elegans.

Previous studies have shown that the development of the vulva of the C. elegans hermaphrodite involves six multipotential hypodermal cells as well as the gonadal anchor cell, which induces vulval formation. Our further examination of the interactions among these seven cells has led to the following model.

Identification and characterization of 22 genes that affect the vulval cell lineages of the nematode Caenorhabditis elegans.

Ninety-five mutants of the nematode Caenorhabditis elegans altered in the cell lineages of the vulva have been isolated on the basis of their displaying one of two phenotypes, Vulvaless or Multivulva. In Vulvaless mutants, which define 12 genes, no vulva is present. In Multivulva mutants, which define ten genes, one or more supernumerary vulva-like protrusions are located along the ventral side of the animal.

Heterochronic mutants of the nematode Caenorhabditis elegans.

Mutations in the Caenorhabditis elegans genes lin-14, lin-28, and lin-29 cause heterochronic developmental defects: the timing of specific developmental events in several tissues is altered relative to the timing of events in other tissues. These defects result from temporal transformations in the fates of specific cells, that is, certain cells express fates normally expressed by cells generated at other developmental stages. The identification and characterization of genes that can be mutated to cause heterochrony support the proposal that heterochrony is a mechanism for phylogenetic change and suggest cellular and genetic bases for heterochronic variation.

The lin-12 locus specifies cell fates in Caenorhabditis elegans.

We describe two classes of mutations in the lin-12 locus of the nematode Caenorhabditis elegans. Ten semidominant mutations (lin-12[d]) appear to elevate the level of lin-12 activity. Thirty-two recessive alleles (lin-12[0]), including two amber mutations, appear to eliminate gene activity.

Egg-laying defective mutants of the nematode Caenorhabditis elegans.

We have isolated 145 fertile mutants of C. elegans that are defective in egg laying and have characterized 59 of them genetically, behaviorally and pharmacologically. These 59 mutants define 40 new genes called egl.

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

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.

Dominant suppressors of a muscle mutant define an essential gene of Caenorhabditis elegans.

The sup-11 1 locus of C. elegans was defined by rare dominant suppressors of unc-93(e1500) III, a mutation that affects muscle structure. All ten of these dominant suppressors have a recessive "scrawny" phenotype.

Serotonin and octopamine in the nematode Caenorhabditis elegans.

The biogenic amines serotonin and octopamine are present in the nematode Caenorhabditis elegans. Serotonin, detected histochemically in whole mounts, is localized in two pharyngeal neurons that appear to be neurosecretory. Octopamine, identified radioenzymatically in crude extracts, probably is also localized in a few neurons.

Nematode postembryonic cell lineages.

The complete postembryonic ceil lineages of the free-living nentatodes Caenorhabditis elegans and Panagrellus redivivus are known. Postembryonic cell divisions lead to substantial increases in the number of cells and, in most cases, in the number of types of cells in the neuronal, muscular, hypodermal, and digestive systems. The patterns of postembyronic cell divisions are essentially invariant and generate a fixed number of progeny cells of strictly specified fates.

Mutations that lead to reiterations in the cell lineages of C. elegans.

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.

Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans.

Twenty-four mutants that alter the normally invariant post-embryonic cell lineages of the nematode Caenorhabditis elegans have been isolated and genetically characterized. In some of these mutants, cell divisions fail that occur in wild-type animals; in other mutants, cells divide that do not normally do so. The mutants differ in the specificities of their defects, so that it is possible to identify mutations that affect some cell lineages but not others.

unc-93(e1500): A behavioral mutant of Caenorhabditis elegans that defines a gene with a wild-type null phenotype.

The uncoordinated, egg-laying-defective mutation, unc-93(e1500) III, of the nematode Caenorhabditis elegans spontaneously reverts to a wild-type phenotype. We describe 102 spontaneous and mutagen-induced revertants that define three loci, two extragenic (sup-9 II and sup-10 X) and one intragenic. Genetic analysis suggests that e1500 is a rare visible allele that generates a toxic product and that intragenic reversion, resulting from the generation of null alleles of the unc-93 gene, eliminates the toxic product.