The terminal differentiation factor LIN-29 is required for proper vulval morphogenesis and egg laying in Caenorhabditis elegans

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4333-4342 ◽  
Author(s):  
J.C. Bettinger ◽  
S. Euling ◽  
A.E. Rougvie
Keyword(s):  
Caenorhabditis Elegans ◽  
Terminal Differentiation ◽  
Egg Laying ◽  
Small Subset ◽  
Wild Type ◽  
Vulval Development ◽  
Genetic Mosaics ◽  
Hypodermal Cell ◽  
Heterochronic Gene ◽  
Final Molt

Caenorhabditis elegans vulval development culminates during exit from the L4-to-adult molt with the formation of an opening through the adult hypodermis and cuticle that is used for egg laying and mating. Vulva formation requires the heterochronic gene lin-29, which triggers hypodermal cell terminal differentiation during the final molt. lin-29 mutants are unable to lay eggs or mate because no vulval opening forms; instead, a protrusion forms at the site of the vulva. We demonstrate through analysis of genetic mosaics that lin-29 is absolutely required in a small subset of lateral hypodermal seam cells, adjacent to the vulva, for wild-type vulva formation and egg laying. However, lin-29 function is not strictly limited to the lateral hypodermis. First, LIN-29 accumulates in many non-hypodermal cells with known roles in vulva formation or egg laying. Second, animals homozygous for one lin-29 allele, ga94, have the vulval defect and cannot lay eggs, despite having a terminally differentiated adult lateral hypodermis. Finally, vulval morphogenesis and egg laying requires lin-29 activity within the EMS lineage, a lineage that does not generate hypodermal cells.

The heterochronic gene lin-29 encodes a zinc finger protein that controls a terminal differentiation event in Caenorhabditis elegans

Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2491-2500 ◽  
Author(s):  
A.E. Rougvie ◽  
V. Ambros
Keyword(s):  
Caenorhabditis Elegans ◽  
Zinc Finger Protein ◽  
Terminal Differentiation ◽  
Regulatory Sequences ◽  
Larval Stages ◽  
Heterochronic Gene ◽  
Final Molt ◽  
Differentiation Event

A hierarchy of heterochronic genes, lin-4, lin-14, lin-28 and lin-29, temporally restricts terminal differentiation of Caenorhabditis elegans hypodermal seam cells to the final molt. This terminal differentiation event involves cell cycle exit, cell fusion and the differential regulation of genes expressed in the larval versus adult hypodermis. lin-29 is the most downstream gene in the developmental timing pathway and thus it is the most direct known regulator of these diverse processes. We show that lin-29 encodes a protein with five zinc fingers of the (Cys)2-(His)2 class and thus likely controls these processes by regulating transcription in a stage-specific manner. Consistent with this role, a lin-29 fusion protein binds in vitro to the 5′ regulatory sequences necessary in vivo for expression of col-19, a collagen gene expressed in the adult hypodermis. lin-29 mRNA is detected in the first larval stage and increases in abundance through subsequent larval stages until the final molt, when lin-29 activity is required for terminal differentiation.

A normally attractive cell interaction is repulsive in two C. elegans mesodermal cell migration mutants

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 797-803 ◽  
Author(s):  
M.J. Stern ◽  
H.R. Horvitz
Keyword(s):  
Cell Migration ◽  
Caenorhabditis Elegans ◽  
Premature Termination ◽  
Cell Interaction ◽  
Egg Laying ◽  
Wild Type ◽  
Mesodermal Cell ◽  
C Elegans ◽  
Somatic Gonad ◽  
Sex Myoblasts

In wild-type Caenorhabditis elegans hermaphrodites, two bilaterally symmetric sex myoblasts (SMs) migrate anteriorly to flank the precise center of the gonad, where they divide to generate the muscles required for egg laying (J. E. Sulston and H. R. Horvitz (1977) Devl Biol. 56, 110–156). Although this migration is largely independent of the gonad, a signal from the gonad attracts the SMs to their precise final positions (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041–1052). Here we show that mutations in either of two genes, egl-15 and egl-17, cause the premature termination of the migrations of the SMs. This incomplete migration is caused by the repulsion of the SMs by the same cells in the somatic gonad that are the source of the attractive signal in wild-type animals.

scholarly journals unc-93(e1500): A BEHAVIORAL MUTANT OF CAENORHABDITIS ELEGANS THAT DEFINES A GENE WITH A WILD-TYPE NULL PHENOTYPE

Genetics ◽  
1980 ◽  
Vol 96 (1) ◽  
pp. 147-164 ◽  
Author(s):  
Iva S Greenwald ◽  
H Robert Horvitz
Keyword(s):  
Caenorhabditis Elegans ◽  
Egg Laying ◽  
Null Alleles ◽  
Wild Type ◽  
Nematode Caenorhabditis Elegans ◽  
Genetic Manipulations ◽  
Wild Type Phenotype ◽  
Toxic Product ◽  
Extragenic Suppressors ◽  
Regulatory Functions

ABSTRACT 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.

scholarly journals The ncl-1 gene and genetic mosaics of Caenorhabditis elegans.

Genetics ◽  
1995 ◽  
Vol 141 (3) ◽  
pp. 989-1006 ◽  
Author(s):  
E M Hedgecock ◽  
R K Herman
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Embryonic Cell ◽  
Vulval Development ◽  
Genetic Mosaics ◽  
Cell Divisions ◽  
Mosaic Analysis ◽  
A Cell ◽  
Intercellular Signal

Abstract A ncl-1 mutation results in enlarged nucleoli, which can be detected in nearly all cells of living animals by Nomarski microscopy. Spontaneous mitotic loss of a ncl-1(+)-containing free duplication in an otherwise homozygous ncl-1 mutant animal results in mosaicism for ncl-1 expression, and the patterns of mosaicism lead us to conclude that ncl-1 acts cell autonomously. The probability of mitotic loss of the duplication sDp3 is approximately constant over many cell divisions. About 60% of the losses of sDp3 at the first embryonic cell division involve nondisjunction. Frequencies of mitotic loss of different ncl-1(+)-bearing free duplications varied over a 200-fold range. The frequencies of mitotic loss were enhanced by a chromosomal him-10 mutation. We have used ncl-1 as a cell autonomous marker in the mosaic analysis of dpy-1 and lin-37. The focus of action of dpy-1 is in hypodermis. A mutation in lin-37 combined with a mutation in another gene results in a synthetic multivulva phenotype. We show that lin-37 acts cell nonautonomously and propose that it plays a role, along with the previously studied gene lin-15, in the generation of an intercellular signal by hyp7 that represses vulval development.

scholarly journals The lin-11 LIM domain transcription factor is necessary for morphogenesis of C. elegans uterine cells

Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5319-5326 ◽  
Author(s):  
A.P. Newman ◽  
G.Z. Acton ◽  
E. Hartwieg ◽  
H.R. Horvitz ◽  
P.W. Sternberg
Keyword(s):  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Egg Laying ◽  
Wild Type ◽  
Lim Domain ◽  
C Elegans ◽  
Expression Studies ◽  
Vulval Precursor Cells ◽  
Cell Induction ◽  
Anchor Cell

The Caenorhabditis elegans hermaphrodite egg-laying system comprises several tissues, including the uterus and vulva. lin-11 encodes a LIM domain transcription factor needed for certain vulval precursor cells to divide asymmetrically. Based on lin-11 expression studies and the lin-11 mutant phenotype, we find that lin-11 is also required for C. elegans uterine morphogenesis. Specifically, lin-11 is expressed in the ventral uterine intermediate precursor (pi) cells and their progeny (the utse and uv1 cells), which connect the uterus to the vulva. Like (pi) cell induction, the uterine lin-11 expression responds to the uterine anchor cell and the lin-12-encoded receptor. In wild type animals, the utse, which forms the planar process at the uterine-vulval interface, fuses with the anchor cell. We found that, in lin-11 mutants, utse differentiation was abnormal, the utse failed to fuse with the anchor cell and a functional uterine-vulval connection was not made. These findings indicate that lin-11 is essential for uterine-vulval morphogenesis.

Stage-specific accumulation of the terminal differentiation factor LIN-29 during Caenorhabditis elegans development

Development ◽  
1996 ◽  
Vol 122 (8) ◽  
pp. 2517-2527 ◽  
Author(s):  
J.C. Bettinger ◽  
K. Lee ◽  
A.E. Rougvie
Keyword(s):  
Caenorhabditis Elegans ◽  
Larval Stage ◽  
Terminal Differentiation ◽  
Loss Of Function ◽  
Cell Nuclei ◽  
Zinc Finger Transcription Factor ◽  
Gene Pathway ◽  
Seam Cell ◽  
Specific Accumulation ◽  
Heterochronic Gene

The Caenorhabditis elegans gene lin-29 is required for the terminal differentiation of the lateral hypodermal seam cells during the larval-to-adult molt. We find that lin-29 protein accumulates in the nuclei of these cells, consistent with its predicted role as a zinc finger transcription factor. The earliest detectable LIN-29 accumulation in seam cell nuclei is during the last larval stage (L4), following the final seam cell division, which occurs during the L3-to-L4 molt. LIN-29 accumulates in all hypodermal nuclei during the L4 stage. The time of LIN-29 appearance in the hypodermis is controlled by the heterochronic gene pathway: LIN-29 accumulates in the hypodermis abnormally early, during the third larval stage, in loss-of-function lin-14, lin-28 and lin-42 mutants, and fails to accumulate in hypodermis of lin-4 mutants. LIN-29 also accumulates stage-specifically in the nuclei of a variety of non-hypodermal cells during development. Its accumulation is dependent upon the upstream heterochronic genes in some, but not all, of these non-hypodermal cells.

The effects of amidantel (BAY d 8815) and its deacylated derivative (BAY d 9216) on wild-type and resistant mutants of Caenorhabditis elegans

1986 ◽  
Vol 64 (6) ◽  
pp. 1310-1316 ◽  
Author(s):  
Robin A. Woods ◽  
Kathleen M. B. Malone ◽  
Cheryl A. Albuquerque ◽  
George Tomlinson
Keyword(s):  
Caenorhabditis Elegans ◽  
Acetylcholine Receptors ◽  
Egg Laying ◽  
Reproductive Capacity ◽  
Similar Amount ◽  
Wild Type ◽  
Drug Induced ◽  
Resistant Mutants ◽  
Anthelmintic Drugs

The anthelmintic drugs amidantel (BAY d 8815) and its deacylated derivative (BAY d 9216) inhibited the growth of wild-type (N2) Caenorhabditis elegans but had little effect on development or reproductive capacity. Inhibition of growth correlated well with drug-induced paralysis, both becoming maximal at around 1.0 mM concentration of either drug. Egg laying was delayed by about 24 h and the rate of laying was only about 60–70% of the controls. However, the period during which eggs were laid was extended by a similar amount and the total number of eggs laid was the same for controls and drug-treated worms. Five drug-resistant mutants (T114, T22, T26, T216, and T226) were isolated following ethylmethanesulphonate mutagenesis. All were shorter than N2 at 96 h on drug-free medium; their growth was not further impaired by either of the anthelmintic drugs. All except T114 exhibited a normal pattern of sexual maturation. Cultures of T114 at 96 h contained many immature worms. This mutant also exhibited the most impaired motility, being severely uncoordinated in liquid suspension. The other mutants could swim normally but were noticeably slower than N2. Genetic analysis indicated that each mutant was the result of a single genetic lesion, that the mutants were recessive, and that there were two genes for amidantel resistance (adt1 and adt2). In vitro studies on representatives of each class (T114 and T22) indicated a defect in the acetylcholine receptor. T22 mutants showed a moderate decrease in sensitivity towards typical cholinergic agonists as well as the anthelmintic drugs, while T114 mutants were apparently devoid of functional pharmacological acetylcholine receptors.

scholarly journals Identification of Heterochronic Mutants in Caenorhabditis elegans: Temporal Misexpression of a Collagen::Green Fluorescent Protein Fusion Gene

Genetics ◽  
1998 ◽  
Vol 149 (3) ◽  
pp. 1335-1351
Author(s):  
Juan E Abrahante ◽  
Eric A Miller ◽  
Ann E Rougvie
Keyword(s):  
Green Fluorescent Protein ◽  
Caenorhabditis Elegans ◽  
Fluorescent Protein ◽  
Fusion Gene ◽  
Terminal Differentiation ◽  
Protein Fusion ◽  
Gene Pathway ◽  
Seam Cell ◽  
Heterochronic Gene ◽  
Green Fluorescent

Abstract The heterochronic genes lin-4, lin-14, lin-28, and lin-29 specify the timing of lateral hypodermal seam cell terminal differentiation in Caenorhabditis elegans. We devised a screen to identify additional genes involved in this developmental timing mechanism based on identification of mutants that exhibit temporal misexpression from the col-19 promoter, a downstream target of the heterochronic gene pathway. We fused the col-19 promoter to the green fluorescent protein gene (gfp) and demonstrated that hypodermal expression of the fusion gene is adult-specific in wild-type animals and temporally regulated by the heterochronic gene pathway. We generated a transgenic strain in which the col-19::gfp fusion construct is not expressed because of mutation of lin-4, which prevents seam cell terminal differentiation. We have identified and characterized 26 mutations that restore col-19::gfp expression in the lin-4 mutant background. Most of the mutations also restore other aspects of the seam cell terminal differentiation program that are defective in lin-4 mutant animals. Twelve mutations are alleles of three previously identified genes known to be required for proper timing of hypodermal terminal differentiation. Among these are four new alleles of lin-42, a heterochronic gene for which a single allele had been described previously. Two mutations define a new gene, lin-58. When separated from lin-4, the lin-58 mutations cause precocious seam cell terminal differentiation and thus define a new member of the heterochronic gene pathway.

scholarly journals The multivulva phenotype of certain Caenorhabditis elegans mutants results from defects in two functionally redundant pathways.

Genetics ◽  
1989 ◽  
Vol 123 (1) ◽  
pp. 109-121 ◽  
Author(s):  
E L Ferguson ◽  
H R Horvitz
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Lineage ◽  
Gene Families ◽  
Precursor Cells ◽  
Wild Type ◽  
Vulval Development ◽  
Vulval Precursor Cells ◽  
New Mutations ◽  
Intercellular Signal

Abstract We previously identified Caenorhabditis elegans mutants in which certain of the six vulval precursor cells adopt fates normally expressed by other vulval precursor cells. These mutants define genes that appear to function in the response to an intercellular signal that induces vulval development. The multivulva (Muv) phenotype of one such mutant, CB1322, results from an interaction between two unlinked mutations, lin-8(n111) II and lin-9(n112) III. In this paper, we identify 18 new mutations, which are alleles of eight genes, that interact with either lin-8(n111) or lin-9(n112) to generate a Muv phenotype. None of these 20 mutations alone causes any vulval cell lineage defects. The "silent Muv" mutations fall into two classes; hermaphrodites carrying a mutation of each class are Muv, while hermaphrodites carrying two mutations of the same class have a wild-type vulval phenotype. Our results indicate that the Muv phenotype of these mutants results from defects in two functionally-redundant pathways, thereby demonstrating that redundancy can occur at the level of gene pathways as well as at the level of gene families.

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