scholarly journals Gain-of-Function Mutations of fem-3, a Sex-Determination Gene in Caenorhabditis elegans

Genetics ◽  
1987 ◽  
Vol 115 (1) ◽  
pp. 107-119 ◽  
Author(s):  
M Kathryn Barton ◽  
Timothy B Schedl ◽  
Judith Kimble
Keyword(s):  
Sex Determination ◽  
Germ Line ◽  
Critical Role ◽  
Temperature Shift ◽  
Sensitive Period ◽  
Temperature Sensitive ◽  
Loss Of Function ◽  
Wild Type ◽  
Gain Of Function ◽  
In The Wild

ABSTRACT We have isolated nine gain-of-function (gf) alleles of the sex-determination gene fem-3 as suppressors of feminizing mutations in fem-1 and fem-2. The wild-type fem-3 gene is needed for spermatogenesis in XX self-fertilizing hermaphrodites and for male development in both soma and germ line of XO animals. Loss-of-function alleles of fem-3 transform XX and XO animals into females (spermless hermaphrodites). In contrast, fem-3(gf) alleles masculinize only one tissue, the hermaphrodite germ line. Thus, XX fem-3(gf) mutant animals have a normal hermaphrodite soma, but the germ line produces a vast excess of sperm and no oocytes. All nine fem-3(gf) alleles are temperature sensitive. The temperature-sensitive period is from late L4 to early adult, a period just preceding the first signs of oogenesis. The finding of gain-of-function alleles which confer a phenotype opposite to that of loss-of-function alleles supports the idea that fem-3 plays a critical role in germ-line sex determination. Furthermore, the germ-line specificity of the fem-3(gf) mutant phenotype and the late temperature-sensitive period suggest that, in the wild-type XX hermaphrodite, fem-3 is negatively regulated so that the hermaphrodite stops making sperm and starts making oocytes. Temperature shift experiments also show that, in the germ line, sexual commitment appears to be a continuing process. Spermatogenesis can resume even after oogenesis has begun, and oogenesis can be initiated much later than normal

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.

scholarly journals Identification and Characterization of Genes That Interact With lin-12 in Caenorhabditis elegans

Genetics ◽  
1997 ◽  
Vol 147 (4) ◽  
pp. 1675-1695 ◽  
Author(s):  
Frans E Tax ◽  
James H Thomas ◽  
Edwin L Ferguson ◽  
H Robert Horvitzt
Keyword(s):  
Cell Fate ◽  
Low Frequency ◽  
Signal Transduction Pathway ◽  
Temperature Shift ◽  
Egg Laying ◽  
Null Alleles ◽  
Temperature Sensitive ◽  
Loss Of Function ◽  
Gain Of Function ◽  
Suppressor Mutations

Abstract We identified and characterized 14 extragenic mutations that suppressed the dominant egg-laying defect of certain lin-12 gain-of-function mutations. These suppressors defined seven genes: sup-l7, lag-2, sel-4, sel-5, sel-6, sel-7 and sel-8. Mutations in six of the genes are recessive suppressors, whereas the two mutations that define the seventh gene, lag-2, are semi-dominant suppressors. These suppressor mutations were able to suppress other lin-12 gain-of-function mutations. The suppressor mutations arose at a very low frequency per gene, 10-50 times below the typical loss-of-function mutation frequency. The suppressor mutations in sup1 7 and lag-2 were shown to be rare non-null alleles, and we present evidence that null mutations in these two genes cause lethality. Temperature-shift studies for two suppressor genes, sup1 7and lag-2, suggest that both genes act at approximately the same time as lin-12in specifying a cell fate. Suppressor alleles of six of these genes enhanced a temperature-sensitive loss-of-function allele of glp-1, a gene related to lin-12 in structure and function. Our analysis of these suppressors suggests that the majority of these genes are part of a shared lin-12/glp-1 signal transduction pathway, or act to regulate the expression or stability of lin-12 and glp-1.

scholarly journals fog-1, a regulatory gene required for specification of spermatogenesis in the germ line of Caenorhabditis elegans.

Genetics ◽  
1990 ◽  
Vol 125 (1) ◽  
pp. 29-39 ◽  
Author(s):  
M K Barton ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Germ Line ◽  
Regulatory Gene ◽  
Sensitive Period ◽  
Temperature Sensitive ◽  
Wild Type ◽  
Male Germ Line ◽  
Somatic Tissues ◽  
Lines Of Evidence

Abstract In wild-type Caenorhabditis elegans, the XO male germ line makes only sperm and the XX hermaphrodite germ line makes sperm and then oocytes. In contrast, the germ line of either a male or a hermaphrodite carrying a mutation of the fog-1 (feminization of the germ line) locus is sexually transformed: cells that would normally make sperm differentiate as oocytes. However, the somatic tissues of fog-1 mutants remain unaffected. All fog-1 alleles identified confer the same phenotype. The fog-1 mutations appear to reduce fog-1 function, indicating that the wild-type fog-1 product is required for specification of a germ cell as a spermatocyte. Two lines of evidence indicate that a germ cell is determined for sex at about the same time that it enters meiosis. These include the fog-1 temperature sensitive period, which coincides in each sex with first entry into meiosis, and the phenotype of a fog-1; glp-1 double mutant. Experiments with double mutants show that fog-1 is epistatic to mutations in all other sex-determining genes tested. These results lead to the conclusion that fog-1 acts at the same level as the fem genes at the end of the sex determination pathway to specify germ cells as sperm.

Genetic evidence that the sans fille locus is involved in Drosophila sex determination.

Genetics ◽  
1988 ◽  
Vol 120 (1) ◽  
pp. 159-171
Author(s):  
B Oliver ◽  
N Perrimon ◽  
A P Mahowald
Keyword(s):  
Sex Determination ◽  
Dosage Compensation ◽  
Germ Line ◽  
Ovarian Tumors ◽  
Lethal Gene ◽  
Nurse Cells ◽  
Loss Of Function ◽  
Wild Type ◽  
Sex Lethal

Abstract Females homozygous for sans fille1621 (= fs(1)1621) have an abnormal germ line. Instead of producing eggs, the germ-line cells proliferate forming ovarian tumors or excessive numbers of nurse cells. The Sex-lethal gene product(s) regulate the branch point of the dosage compensation and sex determination pathways in the soma. The role of Sex-lethal in the germ line is not clear but the germ line of females homozygous for female sterile Sex-lethal alleles or germ-line clones of loss-of-function alleles are characterized by ovarian tumors. Females heterozygous for sans fille1621 or Sex-lethal are phenotypically wild type with respect to viability and fertility but females trans-heterozygous for sans fille1621 and Sex-lethal show ovarian tumors, somatic sexual transformations, and greatly reduced viability.

scholarly journals ACTIVITY OF THE SEX-DETERMINING GENE tra-2 IS MODULATED TO ALLOW SPERMATOGENESIS IN THE C. ELEGANS HERMAPHRODITE

Genetics ◽  
1986 ◽  
Vol 114 (1) ◽  
pp. 53-76
Author(s):  
Tabitha Doniach
Keyword(s):  
Sex Determination ◽  
Regulatory Genes ◽  
The State ◽  
The Self ◽  
Wild Type ◽  
Gain Of Function ◽  
C Elegans ◽  
Male Development ◽  
In The Wild ◽  
Mode Of Regulation

ABSTRACT In the nematode C. elegans, there are two sexes, the self-fertilizing hermaphrodite (XX) and the male (XO). The hermaphrodite is essentially a female that makes sperm for a brief period before oogenesis. Sex determination in C. elegans is controlled by a pathway of autosomal regulatory genes, the state of which is determined by the X:A ratio. One of these genes, tra-2, is required for hermaphrodite development, but not for male development, because null mutations in tra-2 masculinize XX animals but have no effect on XO males. Dominant, gain-of-function tra-2 mutations have now been isolated that completely feminize the germline of XX animals so that they make only oocytes and no sperm and, thus, are female. Most of the tra-2(dom) mutations do not correspondingly feminize XO animals, so they do not appear to interfere with control by her-1, a gene thought to negatively regulate tra-2 in XO animals. Thus, these mutations appear to cause gain of tra-2 function in the XX animal only. Dosage studies indicate that 5 of 7 tra-2(dom) alleles are hypomorphic, so they do not simply elevate XX tra-2 activity overall. These properties suggest that in the wild type, tra-2 activity is under two types of control: (1) in males, it is inactivated by her-1 to allow male development to occur, and (2) in hermaphrodites, tra-2 is active but transiently inactivated by another, unknown, regulator to allow hermaphrodite spermatogenesis; this mode of regulation is hindered by the tra-2(dom) mutations, thereby resulting in XX females.

scholarly journals fog-2, a germ-line-specific sex determination gene required for hermaphrodite spermatogenesis in Caenorhabditis elegans.

Genetics ◽  
1988 ◽  
Vol 119 (1) ◽  
pp. 43-61 ◽  
Author(s):  
T Schedl ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Sex Determination ◽  
Germ Line ◽  
Negative Regulator ◽  
Loss Of Function ◽  
Wild Type ◽  
Negative Regulators ◽  
Nematode Caenorhabditis Elegans ◽  
Isolation And Characterization

Abstract This paper describes the isolation and characterization of 16 mutations in the germ-line sex determination gene fog-2 (fog for feminization of the germ line). In the nematode Caenorhabditis elegans there are normally two sexes, self-fertilizing hermaphrodites (XX) and males (XO). Wild-type XX animals are hermaphrodite in the germ line (spermatogenesis followed by oogenesis), and female in the soma. fog-2 loss-of-function mutations transform XX animals into females while XO animals are unaffected. Thus, wild-type fog-2 is necessary for spermatogenesis in hermaphrodites but not males. The fem genes and fog-1 are each essential for specification of spermatogenesis in both XX and XO animals. fog-2 acts as a positive regulator of the fem genes and fog-1. The tra-2 and tra-3 genes act as negative regulators of the fem genes and fog-1 to allow oogenesis. Two models are discussed for how fog-2 might positively regulate the fem genes and fog-1 to permit spermatogenesis; fog-2 may act as a negative regulator of tra-2 and tra-3, or fog-2 may act positively on the fem genes and fog-1 rendering them insensitive to the negative action of tra-2 and tra-3.

scholarly journals The mog-1 gene is required for the switch from spermatogenesis to oogenesis in Caenorhabditis elegans.

Genetics ◽  
1993 ◽  
Vol 133 (4) ◽  
pp. 919-931 ◽  
Author(s):  
P L Graham ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Sex Determination ◽  
Germ Cells ◽  
Germ Line ◽  
Loss Of Function ◽  
Wild Type ◽  
Per Se ◽  
Post Transcriptional Regulation ◽  
Germline Sex Determination ◽  
Embryonic Death

Abstract Caenorhabditis elegans hermaphrodites make first sperm, then oocytes. By contrast, animals homozygous for any of six loss-of-function mutations in the gene mog-1 (for masculinization of the germ line) make sperm continuously and do not switch into oogenesis. Therefore, in mog-1 mutants, germ cells that normally would become oocytes are transformed into sperm. By contrast, somatic sexual fates are normal, suggesting that mog-1 plays a germ line-specific role in sex determination. Analyses of double mutants suggest that mog-1 negatively regulates the fem genes and/or fog-1: mog-1; fem and mog-1; fog-1 double mutants all make oocytes rather than sperm. Therefore, we propose that wild-type mog-1 is required in the hermaphrodite germ line for regulation of the switch from spermatogenesis to oogenesis rather than for specification of oogenesis per se. In addition to its role in germline sex determination, maternal mog-1 is required for embryogenesis: most progeny of a mog-1; fem or mog-1; fog-1 mother die as embryos. How might the roles of mog-1 in the sperm/oocyte switch and embryogenesis be linked? Previous work showed that fem-3 is regulated post-transcriptionally to achieve the sperm/oocyte switch. We speculate that mog-1 may function in the post-transcriptional regulation of numerous germ-line RNAs, including fem-3. A loss of mog-1 might inappropriately activate fem-3 and thereby abolish the sperm/oocyte switch; its loss might also lead to misregulation of maternal RNAs and thus embryonic death.

scholarly journals Genes that implement the hermaphrodite mode of dosage compensation in Caenorhabditis elegans.

Genetics ◽  
1989 ◽  
Vol 121 (1) ◽  
pp. 57-76 ◽  
Author(s):  
J D Plenefisch ◽  
L DeLong ◽  
B J Meyer
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Sex Determination ◽  
Dosage Compensation ◽  
Sensitive Period ◽  
Temperature Sensitive ◽  
Single Mutation ◽  
Wild Type ◽  
Linked Gene ◽  
Essential Components

Abstract We report a genetic characterization of several essential components of the dosage compensation process in Caenorhabditis elegans. Mutations in the genes dpy-26, dpy-27, dpy-28, and the newly identified gene dpy-29 disrupt dosage compensation, resulting in elevated X-linked gene expression in XX animals and an incompletely penetrant maternal-effect XX-specific lethality. These dpy mutations appear to cause XX animals to express each set of X-linked genes at a level appropriate for XO animals. XO dpy animals are essentially wild type. Both the viability and the level of X-linked gene expression in XX animals carrying mutations in two or more dpy genes are the same as in animals carrying only a single mutation, consistent with the view that these genes act together in a single process (dosage compensation). To define a potential time of action for the gene dpd-28 we performed reciprocal temperature-shift experiments with a heat sensitive allele. The temperature-sensitive period for lethality begins 5 hr after fertilization at the 300-cell stage and extends to about 9 hr, a point well beyond the end of cell proliferation. This temperature-sensitive period suggests that dosage compensation is functioning in XX animals by mid-embryogenesis, when many zygotically transcribed genes are active. While mutations in the dpy genes have no effect on the sexual phenotype of otherwise wild-type XX or XO animals, they do have a slight feminizing effect on animals whose sex-determination process is already genetically perturbed. The opposite directions of the feminizing effects on sex determination and the masculinizing effects on dosage compensation caused by the dpy mutations are inconsistent with the wild-type dpy genes acting to coordinately control both processes. Instead, the feminizing effects are most likely an indirect consequence of disruptions in dosage compensation caused by the dpy mutations. Based on the cumulative evidence, the likely mechanism of dosage compensation in C. elegans involves reducing X-linked gene expression in XX animals to equal that in XO animals via the action of the dpy genes.

scholarly journals Cytosolic Phospholipase A2α–deficient Mice Are Resistant to Collagen-induced Arthritis

2003 ◽  
Vol 197 (10) ◽  
pp. 1297-1302 ◽  
Author(s):  
Martin Hegen ◽  
Linhong Sun ◽  
Naonori Uozumi ◽  
Kazuhiko Kume ◽  
Mary E. Goad ◽  
...  
Keyword(s):  
Critical Role ◽  
Wild Type ◽  
Collagen Induced Arthritis ◽  
Cytosolic Phospholipase ◽  
Severity Scores ◽  
In The Wild ◽  
Cytosolic Phospholipase A2α ◽  
Antibody Levels ◽  
Deficient Mice

Pathogenic mechanisms relevant to rheumatoid arthritis occur in the mouse model of collagen-induced arthritis (CIA). Cytosolic phospholipase A2α (cPLA2α) releases arachidonic acid from cell membranes to initiate the production of prostaglandins and leukotrienes. These inflammatory mediators have been implicated in the development of CIA. To test the hypothesis that cPLA2α plays a key role in the development of CIA, we backcrossed cPLA2α-deficient mice on the DBA/1LacJ background that is susceptible to CIA. The disease severity scores and the incidence of disease were markedly reduced in cPLA2α-deficient mice compared with wild-type littermates. At completion of the study, >90% of the wild-type mice had developed disease whereas none of the cPLA2α-deficient mice had more than one digit inflamed. Furthermore, visual disease scores correlated with severity of disease determined histologically. Pannus formation, articular fibrillation, and ankylosis were all dramatically reduced in the cPLA2α-deficient mice. Although the disease scores differed significantly between cPLA2α mutant and wild-type mice, anti-collagen antibody levels were similar in the wild-type mice and mutant littermates. These data demonstrate the critical role of cPLA2α in the pathogenesis of CIA.

A new class of mutations in Arabidopsis thaliana, acaulis1, affecting the development of both inflorescences and leaves

Development ◽  
1993 ◽  
Vol 118 (3) ◽  
pp. 751-764 ◽  
Author(s):  
H. Tsukaya ◽  
S. Naito ◽  
G. P. Redei ◽  
Y. Komeda
Keyword(s):  
Arabidopsis Thaliana ◽  
Apical Meristem ◽  
Developmental Stages ◽  
Temperature Shift ◽  
Wild Type ◽  
New Class ◽  
Group 4 ◽  
Consequent Reduction ◽  
In The Wild ◽  
Specific Temperature

We isolated and analyzed mutants of Arabidopsis thaliana, acaulis, with flower stalks that are almost absent or are much reduced in length. The mutations are divided between two loci, acaulis1 (acl1) and acaulis2 (acl2). The acl1-1 mutation has been assigned to linkage group 4 in the vicinity of locus ap2. The acl1-1 mutant showed premature arrest of the inflorescence meristem after the onset of reproductive development, followed by consequent reduction in the number of flower-bearing phytomers and therefore flowers. The apical meristem of the inflorescences was morphologically normal but its radius was about half that of the wild type. The acl1 mutants are also defective in the development of foliage leaves. Both defects could be rescued by growth at a specific temperature (28°C). The length of the cells in acl1-3 mutant was less than that in the wild type but the numbers of cells in leaves and internodes of acl1 mutants were calculated to be the same as those of the wild type. Thus, the defects in inflorescences and leaves were attributed to defects in the process of elongation (maturation) of these cells. Temperature-shift experiments showed that the Acl1+ product was necessary at all developmental stages. A critical stage was shown to exist for recovery from the cessation of development of inflorescence meristems that was caused by the acl1-1 mutation. Grafting experiments showed that the acl1-1 mutation does not affect diffusible substances. An analysis of double mutants carrying both acl1-1 and one of developmental mutations, ap1, clv1, lfy, or tfl1, showed that ACL1 is a new class of gene.

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