Dominant maternal-effect mutations causing embryonic lethality in Caenorhabditis elegans.

Genetics ◽  
1990 ◽  
Vol 125 (2) ◽  
pp. 351-369 ◽  
Author(s):  
P E Mains ◽  
I A Sulston ◽  
W B Wood
Keyword(s):  
Caenorhabditis Elegans ◽  
Maternal Effect ◽  
Gene Dosage ◽  
Recessive Mutation ◽  
Dominant Male ◽  
Temperature Sensitive ◽  
Male Mating ◽  
Loss Of Function ◽  
Dominant Mutant ◽  
Embryonic Viability

Abstract We undertook screens for dominant, temperature-sensitive, maternal-effect embryonic-lethal mutations of Caenorhabditis elegans as a way to identify certain classes of genes with early embryonic functions, in particular those that are members of multigene families and those that are required in two copies for normal development. The screens have identified eight mutations, representing six loci. Mutations at three of the loci result in only maternal effects on embryonic viability. Mutations at the remaining three loci cause additional nonmaternal (zygotic) effects, including recessive lethality or sterility and dominant male mating defects. Mutations at five of the loci cause visible pregastrulation defects. Three mutations appear to be allelic with a recessive mutation of let-354. Gene dosage experiments indicate that one mutation may be a loss-of-function allele at a haploin sufficient locus. The other mutations appear to result in gain-of-function "poison" gene products. Most of these become less deleterious as the relative dosage of the corresponding wild-type allele is increased; we show that relative self-progeny viabilities for the relevant hermaphrodite genotypes are generally M/+/+ greater than M/+ greater than M/M/+ greater than M/Df greater than M/M, where M represents the dominant mutant allele.

A Limited Number of Caenorhabditis elegans Genes Are Readily Mutable to Dominant, Temperature-Sensitive Maternal-Effect Embryonic Lethality

Genetics ◽  
1997 ◽  
Vol 147 (4) ◽  
pp. 1665-1674 ◽  
Author(s):  
Nancy L Mitenko ◽  
James R Eisner ◽  
John R Swiston ◽  
Paul E Mains
Keyword(s):  
Caenorhabditis Elegans ◽  
Maternal Effect ◽  
Temperature Sensitive ◽  
Loss Of Function ◽  
Gain Of Function ◽  
C Elegans ◽  
Lethal Mutations ◽  
Embryonic Lethal ◽  
Embryonic Lethal Mutations ◽  
Dominant Temperature Sensitive

Abstract Dominant gain-of-function mutations can give unique insights into the study of gene function. In addition, gain-of-function mutations, unlike loss-of-function alleles, are not biased against the identification of genetically redundant loci. To identify novel genetic functions active during Caenorhabditis elegans embryogenesis, we have collected a set of dominant temperature-sensitive maternal-effect embryonic lethal mutations. In a previous screen, we isolated eight such mutations, distributed among six genes. In the present study, we describe eight new dominant mutations that identify only three additional genes, yielding a total of 16 dominant mutations found in nine genes. Therefore, it appears that a limited number of C. elegans genes mutate to this phenotype at appreciable frequencies. Five of the genes that we identified by dominant mutations have loss-of-function alleles. Two of these genes may lack loss-of-function phenotypes, indicating that they are nonessential and so may represent redundant loci. Loss-of-function mutations of three other genes are associated with recessive lethality, indicating nonredundancy.

scholarly journals Mutations affecting the meiotic and mitotic divisions of the early Caenorhabditis elegans embryo.

Genetics ◽  
1990 ◽  
Vol 126 (3) ◽  
pp. 593-605 ◽  
Author(s):  
P E Mains ◽  
K J Kemphues ◽  
S A Sprunger ◽  
I A Sulston ◽  
W B Wood
Keyword(s):  
Caenorhabditis Elegans ◽  
Maternal Effect ◽  
Mutant Gene ◽  
Temperature Sensitive ◽  
Loss Of Function ◽  
Gain Of Function ◽  
Lethal Mutations ◽  
Cell Embryo ◽  
New Gene ◽  
The One

Abstract We describe interactions between maternal-effect lethal mutations in four genes of Caenorhabditis elegans whose products appear to be involved in the meiotic and mitotic divisions of the one-cell embryo. Mitosis is disrupted by two dominant temperature-sensitive gain-of-function maternal-effect lethal mutations, mei-1(ct46) and mel-26(ct61), and by recessive loss-of-function maternal-effect lethal mutations of zyg-9. The phenotypic defects resulting from these mutations are similar. Doubly mutant combinations show a strong enhancement of the maternal-effect lethality under semipermissive conditions, suggesting that the mutant gene products interact. We isolated 15 dominant suppressors of the gain-of-function mutation mei-1(ct46). Thirteen of these suppressors are apparently intragenic, but 11 of them suppress in trans as well as cis. Two extragenic suppressors define a new gene, mei-2. The suppressor mutations in these two genes also result in recessive maternal-effect lethality, but with meiotic rather than mitotic defects. Surprisingly, most of these suppressors are also able to suppress mel-26(ct61) in addition to mei-1(ct46). The products of the four genes mei-1, mei-2, zyg-9 and mel-26 could be responsible for some of the specialized features that distinguish the meiotic from the mitotic divisions in the one-cell embryo.

scholarly journals Dominant unc-37 mutations suppress the movement defect of a homeodomain mutation in unc-4, a neural specificity gene in Caenorhabditis elegans.

Genetics ◽  
1993 ◽  
Vol 135 (3) ◽  
pp. 741-753 ◽  
Author(s):  
D M Miller ◽  
C J Niemeyer ◽  
P Chitkara
Keyword(s):  
Caenorhabditis Elegans ◽  
Motor Neurons ◽  
Synaptic Input ◽  
Neuronal Morphology ◽  
Axonal Guidance ◽  
Temperature Sensitive ◽  
Homeodomain Protein ◽  
Loss Of Function ◽  
Selection Scheme ◽  
Synaptic Specificity

Abstract The unc-4 gene of Caenorhabditis elegans encodes a homeodomain protein that defines synaptic input to ventral cord motor neurons. unc-4 mutants are unable to crawl backward because VA motor neurons are miswired with synaptic connections normally reserved for their sister cells, the VB motor neurons. These changes in connectivity are not accompanied by any visible effects upon neuronal morphology, which suggests that unc-4 regulates synaptic specificity but not axonal guidance or outgrowth. In an effort to identify other genes in the unc-4 pathway, we have devised a selection scheme for rare mutations that suppress the Unc-4 phenotype. We have isolated four, dominant, extragenic, allele-specific suppressors of unc-4(e2322ts), a temperature sensitive allele with a point mutation in the unc-4 homeodomain. Our data indicate that these suppressors are gain-of-function mutations in the previously identified unc-37 gene. We show that the loss-of-function mutation unc-37(e262) phenocopies the Unc-4 movement defect but does not prevent unc-4 expression or alter VA motor neuron morphology. These findings suggest that unc-37 functions with unc-4 to specify synaptic input to the VA motor neurons. We propose that unc-37 may be regulated by unc-4. Alternatively, unc-37 may encode a gene product that interacts with the unc-4 homeodomain.

Patterning of dopaminergic neurotransmitter identity among Caenorhabditis elegans ray sensory neurons by a TGFbeta family signaling pathway and a Hox gene

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5819-5831 ◽  
Author(s):  
R. Lints ◽  
S.W. Emmons
Keyword(s):  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Signaling Pathway ◽  
Cell Fate ◽  
Sensory Neurons ◽  
Ectopic Expression ◽  
Temperature Shift ◽  
Temperature Sensitive ◽  
Loss Of Function ◽  
Hox Gene

We have investigated the mechanism that patterns dopamine expression among Caenorhabditis elegans male ray sensory neurons. Dopamine is expressed by the A-type sensory neurons in three out of the nine pairs of rays. We used expression of a tyrosine hydroxylase reporter transgene as well as direct assays for dopamine to study the genetic requirements for adoption of the dopaminergic cell fate. In loss-of-function mutants affecting a TGFbeta family signaling pathway, the DBL-1 pathway, dopaminergic identity is adopted irregularly by a wider subset of the rays. Ectopic expression of the pathway ligand, DBL-1, from a heat-shock-driven transgene results in adoption of dopaminergic identity by rays 3–9; rays 1 and 2 are refractory. The rays are therefore prepatterned with respect to their competence to be induced by a DBL-1 pathway signal. Temperature-shift experiments with a temperature-sensitive type II receptor mutant, as well as heat-shock induction experiments, show that the DBL-1 pathway acts during an interval that extends from two to one cell generation before ray neurons are born and begin to differentiate. In a mutant of the AbdominalB class Hox gene egl-5, rays that normally express EGL-5 do not adopt dopaminergic fate and cannot be induced to express DA when DBL-1 is provided by a heat-shock-driven dbl-1 transgene. Therefore, egl-5 is required for making a subset of rays capable of adopting dopaminergic identity, while the function of the DBL-1 pathway signal is to pattern the realization of this capability.

scholarly journals LETHALS, STERILES AND DEFICIENCIES IN A REGION OF THE X CHROMOSOME OF CAENORHABDITIS ELEGANS

Genetics ◽  
1979 ◽  
Vol 92 (1) ◽  
pp. 99-115 ◽  
Author(s):  
Philip M Meneely ◽  
Robert K Herman
Keyword(s):  
Caenorhabditis Elegans ◽  
X Chromosome ◽  
Maternal Effect ◽  
Mutant Allele ◽  
Temperature Sensitive ◽  
Wild Type ◽  
Nematode Caenorhabditis Elegans ◽  
X Chromosomes ◽  
X Ray ◽  
Chromosome Duplication

ABSTRACT Twenty-one X-linked recessive lethal and sterile mutations balanced by an unlinked X-chromosome duplication have been identified following EMS treatment of the small nematode, Caenorhabditis elegans. The mutations have been assigned by complementation analysis to 14 genes, four of which have more than one mutant allele. Four mutants, all alleles, are temperature-sensitive embryonic lethals. Twelve mutants, in ten genes, are early larval lethals. TWO mutants are late larval lethals, and the expression of one of these is influenced by the number of X chromosomes in the genotype. Two mutants are maternal-effect lethals; for both, oocytes made by mutant hermaphrodites are rescuable by wild-type sperm. One of the maternal-effect lethals and two larval lethals are allelic. One mutant makes defective sperm. The lethals and steriles have been mapped by recombination and by complementation testing against 19 deficiencies identified after X-ray treatment. The deficiencies divide the region, about 15% of the X-chromosome linkage map, into at least nine segments. The deficiencies have also been used to check the phenotypes of hemizygous lethal and sterile hermaphrodites.

scholarly journals Analysis of the role of tra-1 in germline sex determination in the nematode Caenorhabditis elegans.

Genetics ◽  
1989 ◽  
Vol 123 (4) ◽  
pp. 755-769 ◽  
Author(s):  
T Schedl ◽  
P L Graham ◽  
M K Barton ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Sex Determination ◽  
Germ Line ◽  
Temperature Sensitive ◽  
Loss Of Function ◽  
Wild Type ◽  
Allelic Series ◽  
Isolation And Characterization ◽  
Somatic Gonad

Abstract In wild-type Caenorhabditis elegans there are two sexes, self-fertilizing hermaphrodites (XX) and males (XO). To investigate the role of tra-1 in controlling sex determination in germline tissue, we have examined germline phenotypes of nine tra-1 loss-of-function (lf) mutations. Previous work has shown that tra-1 is needed for female somatic development as the nongonadal soma of tra-1(lf) XX mutants is masculinized. In contrast, the germline of tra-1(lf) XX and XO animals is often feminized; a brief period of spermatogenesis is followed by oogenesis, rather than the continuous spermatogenesis observed in wild-type males. In addition, abnormal gonadal (germ line and somatic gonad) phenotypes are observed which may reflect defects in development or function of somatic gonad regulatory cells. Analysis of germline feminization and abnormal gonadal phenotypes of the various mutations alone or in trans to a deficiency reveals that they cannot be ordered in an allelic series and they do not converge to a single phenotypic endpoint. These observations lead to the suggestion that tra-1 may produce multiple products and/or is autoregulated. One interpretation of the germline feminization is that tra-1(+) is necessary for continued specification of spermatogenesis in males. We also report the isolation and characterization of tra-1 gain-of-function (gf) mutations with novel phenotypes. These include temperature sensitive, recessive germline feminization, and partial somatic loss-of-function phenotypes.

Suppressors of a lin-12 hypomorph define genes that interact with both lin-12 and glp-1 in Caenorhabditis elegans.

Genetics ◽  
1993 ◽  
Vol 135 (3) ◽  
pp. 765-783 ◽  
Author(s):  
M Sundaram ◽  
I Greenwald
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Gene Dosage ◽  
Egg Laying ◽  
Loss Of Function ◽  
Cell Fate Decision ◽  
Cell Fates ◽  
Cell Fate Decisions ◽  
Suppressor Mutations ◽  
Fate Decision

Abstract The lin-12 gene of Caenorhabditis elegans is thought to encode a receptor which mediates cell-cell interactions required to specify certain cell fates. Reversion of the egg-laying defective phenotype caused by a hypomorphic lin-12 allele identified rare extragenic suppressor mutations in five genes, sel-1, sel-9, sel-10, sel-11 and sel(ar40) (sel = suppressor and/or enhancer of lin-12). Mutations in each of these sel genes suppress defects associated with reduced lin-12 activity, and enhance at least one defect associated with elevated lin-12 activity. None of the sel mutations cause any obvious phenotype in a wild-type background. Gene dosage experiments suggest that sel-1 and sel(ar40) mutations are reduction-of-function mutations, while sel-9 and sel-11 mutations are gain-of-function mutations. sel-1, sel-9, sel-11 and sel(ar40) mutations do not suppress amorphic lin-12 alleles, while sel-10 mutations are able to bypass partially the requirement for lin-12 activity in at least one cell fate decision. sel-1, sel-9, sel-10, sel-11 and sel(ar40) mutations are also able to suppress the maternal-effect lethality caused by a partial loss-of-function allele of glp-1, a gene that is both structurally and functionally related to lin-12. These sel genes may therefore function in both lin-12 and glp-1 mediated cell fate decisions.

gon-2, a Gene Required for Gonadogenesis in Caenorhabditis elegans

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1077-1089 ◽  
Author(s):  
Andrew Y Sun ◽  
Eric J Lambie
Keyword(s):  
Caenorhabditis Elegans ◽  
Larval Stage ◽  
Cell Lineage ◽  
Temperature Sensitive ◽  
Loss Of Function ◽  
Primary Defect ◽  
Cell Fates ◽  
Fourth Larval Stage ◽  
Full Complement ◽  
Sensitive Allele

The gonad of the Caenorhabditis elegans hermaphrodite is generated by the postembryonic divisions of two somatic precursors, Z1 and Z4, and two germline precursors, Z2 and Z3. These cells begin division midway through the first larval stage. By the end of the fourth larval stage, Z1 and Z4 produce 143 descendants, while Z2 and Z3 give rise to ∼1000 descendants. The divisions of Z2 and Z3 are dependent on signals produced by Z1 and Z4, but not vice versa. We have characterized the properties of five loss-of-function alleles of a newly described gene, which we call gon-2. In gon-2 mutants, gonadogenesis is severely impaired; in some animals, none of the gonad progenitors undergo any postembryonic divisions. Mutations in gon-2 have a partial maternal effect: either maternal or zygotic expression is sufficient to prevent the severe gonadogenesis defects. By cell lineage analysis, we found that the primary defect in gon-2 mutants is a delay (sometimes a complete block) in the onset and continuation of gonadal divisions. The results of upshift experiments using a temperature-sensitive allele suggest that zygotic expression of gon-2 begins early in embryogenesis, before the birth of Z1 and Z4. The results of downshift experiments suggest that Z1 and Z4 can generate the full complement of gonadal tissues even when gon-2 function is inhibited until the end of the second larval stage. Thus, gon-2 activity is probably not required for the specification of gonadal cell fates, but appears to be generally required for gonadal cell divisions.

scholarly journals A novel dominant transformer allele of the sex-determining gene her-1 of Caenorhabditis elegans.

Genetics ◽  
1988 ◽  
Vol 120 (1) ◽  
pp. 145-157
Author(s):  
C Trent ◽  
W B Wood ◽  
H R Horvitz
Keyword(s):  
Caenorhabditis Elegans ◽  
Sexual Identity ◽  
Temperature Sensitive ◽  
Dominant Allele ◽  
Loss Of Function ◽  
Gain Of Function ◽  
C Elegans

Abstract We have characterized a novel dominant allele of the sex-determining gene her-1 of Caenorhabditis elegans. This allele, called n695, results in the incomplete transformation of XX animals into phenotypic males. Previously characterized recessive her-1 alleles transform XO animals into phenotypic hermaphrodites. We have identified five new recessive her-1 mutations as intragenic suppressors of n695. Three of these suppressors are weak, temperature-sensitive alleles. We show that the recessive her-1 mutations are loss-of-function alleles, and that the her-1(n695) mutation results in a gain-of-function at the her-1 locus. The existence of dominant and recessive alleles that cause opposite phenotypic transformations demonstrates that the her-1 gene acts to control sexual identity in C. elegans.

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