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H R Horvitz

Publications and source records attributed to H R Horvitz.

At least 163 records · Page 9Linked to original sources
PubMed1983

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. for egg-laying abnormal. Most of the other mutants are defective in previously identified genes. The egl mutants differ with respect to the severity of their egg-laying defects and the presence of behavioral or morphological pleiotropies. We have defined four distinct categories of mutants based on their responses to the pharmacological agents serotonin and imipramine, which stimulate egg laying by wild-type hermaphrodites. These drugs test the functioning of the vulva, the vulval and uterine muscles and the hermaphrodite-specific neurons (HSNs), which innervate the vulval muscles. Mutants representing 14 egl genes fail to respond to serotonin and to imipramine and are likely to be defective in the functioning of the vulva or the vulval and uterine muscles. Four mutants (representing four different genes) lay eggs in response to serotonin but not to imipramine and appear to be egg-laying defective because of defects in the HSNs; three of these four were selected specifically for these drug responses. Mutants representing seven egl genes lay eggs in response to serotonin and to imipramine. One egl mutant responds to imipramine but not to serotonin. The remaining egl mutants show variable or intermediate responses to the drugs. Two of the HSN-defective mutants, egl-1 and her-1(n695), lack HSN cell bodies and are likely to be expressing the normally male-specific program of HSN cell death. Whereas egl-1 animals appear to be defective specifically in HSN development, her-1(n695) animals exhibit multiple morphological pleiotropies, displaying partial transformation of the sexual phenotype of many cells and tissues. At least two of the egl mutants appear to be defective in the processing of environmental signals that modulate egg laying and may define new components of the neural circuitry that control egg laying.

Animals↗
PubMed1983

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. 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)

Animals↗
PubMed1982

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. Exogenous serotonin and octopamine elicit specific and opposite behavioral responses in Caenorhabditis elegans, suggesting that these compounds function physiologically as antagonists.

Age Factors↗
PubMed1982

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. Two additional classes of sup-11 alleles were identified. One class, null alleles, was obtained by reversion of the dominant suppressor activity. These null alleles are recessive embryonic lethals, indicating that sup-11 is an essential gene. Members of the second class, rare semidominant revertants of the "scrawny" phenotype, are partial suppressors of unc-93(e1500). The genetic properties of the dominant suppressor mutations suggest that they are rare missense mutations that confer a novel activity to the sup-11 protein. We consider some of the ways that sup-11 alleles might suppress unc-93(e1500), including the possibilities that the altered sup-11 proteins restore function to a protein complex or are modified products of a gene that is a member of an unc-93 gene family.

Animals↗
PubMed1981

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. 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.

Animals↗
PubMed1980

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. We propose that the genetic properties of the unc-93 locus, including the spontaneous reversion of the e1500 mutation, indicate that unc-93 may be a member of a multigene family. The extragenic suppressors also appear to arise as the result of elimination of gene activity; these genes may encode regulatory functions or products that interact with the unc-93 gene product. Genes such as unc-93, sup-9 and sup-10 may be useful for genetic manipulations, including the generation of deficiencies and mutagen testing.

Alleles↗
PubMed1980

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. These mutants define 14 complementation groups, which have been mapped. The abnormal phenotype of most of the cell-lineage mutants results from a single recessive mutation; however, the excessive cell divisions characteristic of one strain, CB1322, require the presence of two unlinked recessive mutations. All 24 cell-lineage mutants display incomplete penetrance and/or variable expressivity. Three of the mutants are suppressed by pleiotropic suppressors believed to be specific for null alleles, suggesting that their phenotypes result from the complete absence of gene activity.

Animals↗
PubMed1975

Studies of mutations in T4 control genes 33 and 55.

Available mutations in transcriptional control genes 33 and 55 of coliphage T4 have been examined. By complementation analysis and map position, 15 mutants (13 in T4D, 2 in T4B) have been shown to lie in gene 33 and 6 (5 in T4D, 1 in T4B) in gene 55. According to patterns of suppression and recombination, these mutants define three distinct amber sites in gene 33 and also three distinct amber sites in gene 55. All of these mutations are true amber mutations, in apparent contrast to some traditional T4 "amber" mutants which grow in su+ E. coli CR63 but not in su minus E. coli B because of a strain difference other than the su+ determinant. Evidence is presented that, contrary to previous suggestions (BOLLE et al. 1968; pulitzer and geiduschek 1970), the gene 33 product is absolutely essential for T4 development.

Coliphages↗
PubMedDate not supplied

Signal transduction during C. elegans vulval induction.

Nematode proteins related to the human epidermal growth factor receptor and Ras proteins act in a common pathway to control cell fates in response to an inductive signal. Analysis of these gene products during C. elegans vulval induction allows detailed study of their function in the context of a developing organism.

Amino Acid Sequence↗