scholarly journals Suppressors of glp-1, a gene required for cell communication during development in Caenorhabditis elegans, define a set of interacting genes.

Genetics ◽  
1993 ◽  
Vol 135 (4) ◽  
pp. 1011-1022 ◽  
Author(s):  
E M Maine ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Cell Function ◽  
Germ Line ◽  
Control Cell ◽  
Cell Communication ◽  
Cell Interactions ◽  
Temperature Sensitive ◽  
Allele Specific ◽  
Mitotic Proliferation

Abstract The glp-1 gene is essential for two cell interactions that control cell fate in Caenorhabditis elegans: induction of anterior pharynx in the embryo and induction of mitotic proliferation in the germ line. To identify other genes involved in these cell interactions, we have isolated suppressors of two temperature sensitive alleles of glp-1. Each of 14 recessive suppressors rescues both embryonic and germline glp-1(ts) defects. These suppressors are extragenic and define a set of six genes designated sog, for suppressor of glp-1. Suppression of glp-1 is the only obvious phenotype associated with sog mutations. Mutations in different sog genes show allele-specific intergenic noncomplementation, suggesting that the sog gene products may interact. In addition, we have analyzed a semidominant mutation that suppresses only the glp-1 germline phenotype and has a conditional feminized phenotype of its own. None of the suppressors rescues a glp-1 null mutation and therefore they do not bypass a requirement for glp-1. Distal tip cell function remains necessary for germline proliferation in suppressed animals. These suppressor mutations identify genes that may encode other components of the glp-1 mediated cell-signaling pathway or regulate glp-1 expression.

scholarly journals Genetics of intercellular signalling in C. elegans

Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 53-57
Author(s):  
Judith Austin ◽  
Eleanor M. Maine ◽  
Judith Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Molecular Level ◽  
Cell Interactions ◽  
Nematode Caenorhabditis Elegans ◽  
Developmental Potential ◽  
C Elegans ◽  
Intercellular Signalling ◽  
Mitotic Proliferation ◽  
Cell Cell

Cell–cell interactions play a significant role in controlling cell fate during development of the nematode Caenorhabditis elegans. It has been found that two genes, glp-1 and lin-12, are required for many of these decisions, glp-1 is required for induction of mitotic proliferation in the germline by the somatic distal tip cell and for induction of the anterior pharynx early in embryogenesis. lin-12 is required for the interactions between cells of equivalent developmental potential, which allow them to take on different fates. Comparison of these two genes on a molecular level indicates that they are similar in sequence and organization, suggesting that the mechanisms of these two different sets of cell–cell interactions are similar.

Porcine nuclear transfer using somatic donor cells altered to express male germ cell function

2009 ◽  
Vol 21 (7) ◽  
pp. 882 ◽  
Author(s):  
Sangho Roh ◽  
Hye-Yeon Choi ◽  
Sang Kyu Park ◽  
Cheolhee Won ◽  
Bong-Woo Kim ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Fate ◽  
Nuclear Transfer ◽  
Cell Function ◽  
Control Cell ◽  
Donor Cell ◽  
Male Germ Cell ◽  
Cell Group ◽  
Cell Extracts

Recent studies reported that the direct transformation of one differentiated somatic cell type into another is possible. In the present study, we were able to modulate the cell fate of somatic cells to take on male germ cell function by introducing cell extracts derived from porcine testis tissue. Fibroblasts were treated with streptolysin O, which reversibly permeabilises the plasma membrane, and incubated with testis extracts. Our results showed that the testis extracts (TE) could activate expression of male germ cell-specific genes, implying that TE can provide regulatory components required for altering the cell fate of fibroblasts. Male germ cell function was sustained for more than 10 days after the introduction of TE. In addition, a single TE-treated cell was injected directly into the cytoplasm of in vitro-matured porcine oocytes. The rate of blastocyst formation was significantly higher in the TE-treated nuclear donor cell group than in the control cell group. The expression level of Nanog, Sox9 and Eomes was drastically increased when altered cells were used as donor nuclei. Our results suggest that TE can be used to alter the cell fate of fibroblasts to express male germ cell function and improve the developmental efficiency of the nuclear transfer porcine embryos.

scholarly journals hecd-1 Modulates Notch Activity in Caenorhabditis elegans

2015 ◽  
Vol 5 (3) ◽  
pp. 353-359 ◽  
Author(s):  
Yunting Chen ◽  
Iva Greenwald
Keyword(s):  
Quality Control ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Germ Line ◽  
Notch Pathway ◽  
Cell Fate Decisions ◽  
Notch Activity ◽  
C Elegans ◽  
Somatic Gonad ◽  
Constitutively Active

Abstract Notch is a receptor that mediates cell–cell interactions that specify binary cell fate decisions in development and tissue homeostasis. Inappropriate Notch signaling is associated with cancer, and mutations in Notch pathway components have been associated with developmental diseases and syndromes. In Caenorhabditis elegans, suppressors of phenotypes associated with constitutively active LIN-12/Notch have identified many conserved core components and direct or indirect modulators. Here, we molecularly identify sel(ar584), originally isolated as a suppressor of a constitutively active allele of lin-12. We show that sel(ar584) is an allele of hecd-1, the ortholog of human HECDT1, a ubiquitin ligase that has been implicated in several different mammalian developmental events. We studied interactions of hecd-1 with lin-12 in the somatic gonad and with the other C. elegans Notch gene, glp-1, in the germ line. We found that hecd-1 acts as a positive modulator of lin-12/Notch activity in a somatic gonad context—the original basis for its isolation—but acts autonomously as a negative modulator of glp-1/Notch activity in the germ line. As the yeast ortholog of HECD-1, Ufd4p, has been shown to function in quality control, and C. elegans  HECD-1 has been shown to affect mitochondrial maintenance, we propose that the different genetic interactions between hecd-1 and Notch genes we observed in different cell contexts may reflect differences in quality control regulatory mechanisms or in cellular metabolism.

scholarly journals Ligand-receptor promiscuity enables cellular addressing

2020 ◽  
Author(s):  
Christina J. Su ◽  
Arvind Murugan ◽  
James M. Linton ◽  
Akshay Yeluri ◽  
Justin Bois ◽  
...  
Keyword(s):  
Cell Fate ◽  
Control Cell ◽  
Cell Communication ◽  
Biochemical Parameter ◽  
Cell Types ◽  
Receptor Expression ◽  
Modeling Framework ◽  
Morphogenetic Protein ◽  
Bmp Pathway ◽  
Fate Decision

AbstractIn multicellular organisms, secreted ligands selectively activate, or “address,” specific target cell populations to control cell fate decision-making and other processes. Key cell-cell communication pathways use multiple promiscuously interacting ligands and receptors, provoking the question of how addressing specificity can emerge from molecular promiscuity. To investigate this issue, we developed a general mathematical modeling framework based on the bone morphogenetic protein (BMP) pathway architecture. We find that promiscuously interacting ligand-receptor systems allow a small number of ligands, acting in combinations, to address a larger number of individual cell types, each defined by its receptor expression profile. Promiscuous systems outperform seemingly more specific one-to-one signaling architectures in addressing capacity. Combinatorial addressing extends to groups of cell types, is robust to receptor expression noise, grows more powerful with increasing receptor multiplicity, and is maximized by specific biochemical parameter relationships. Together, these results identify fundamental design principles governing cell addressing by ligand combinations.

scholarly journals The generation and genetic analysis of suppressors of lethal mutations in the Caenorhabditis elegans rol-3(V) gene.

Genetics ◽  
1994 ◽  
Vol 136 (1) ◽  
pp. 129-143 ◽  
Author(s):  
W B Barbazuk ◽  
R C Johnsen ◽  
D L Baillie
Keyword(s):  
Caenorhabditis Elegans ◽  
Genetic Analysis ◽  
Genetic Interaction ◽  
Temperature Sensitive ◽  
Left Hand ◽  
Larval Stages ◽  
Allele Specific ◽  
Complementation Groups ◽  
Nematode Cuticle ◽  
Developmental Role

Abstract The Caenorhabditis elegans rol-3(e754) mutation is a member of a general class of mutations affecting gross morphology, presumably through disruption of the nematode cuticle. Adult worms homozygous for rol-3(e754) exhibit rotation about their long axis associated with a left-hand twisted cuticle, musculature, gut and ventral nerve cord. Our laboratory previously isolated 12 recessive lethal alleles of rol-3. All these lethal alleles cause an arrest in development at either early or mid-larval stages, suggesting that the rol-3 gene product performs an essential developmental function. Furthermore, through the use of the heterochronic mutants lin-14 and lin-29, we have established that the expression of rol-3(e754)'s adult specific visible function is not dependent on the presence of an adult cuticle. In an attempt to understand rol-3's developmental role we sought to identify other genes whose products interact with that of rol-3. Toward this end, we generated eight EMS induced and two gamma irradiation-induced recessive suppressors of the temperature sensitive (ts) mid-larval lethal phenotype of rol-3(s1040ts). These suppressors define two complementation groups srl-1 II and srl-2 III; and, while they suppress the rol-3(s1040) lethality, they do not suppress the adult specific visible rolling phenotype. Furthermore, there is a complex genetic interaction between srl-2 and srl-1 such that srl-2(s2506) fails to complement all srl alleles tested. These results suggest that srl-1 and srl-2 may share a common function and, thus, possibly constitute members of the same gene family. Mutations in both srl-1 and srl-2 produce no obvious hermaphrodite phenotypes in the absence of rol-3(s1040ts); however, males homozygous for either srl-1 or srl-2 display aberrant tail morphology. We present evidence suggesting that the members of srl-2 are not allele specific with respect to their suppression of rol-3 lethality, and that rol-3 may act in some way to influence proper posterior morphogenesis. Finally, based on our genetic analysis of rol-3 and the srl mutations, we present a model whereby the wild-type products of the srl loci act in a concerted manner to negatively regulate the rol-3 gene.

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.

scholarly journals Biology of the Caenorhabditis elegans Germline Stem Cell System

Genetics ◽  
2019 ◽  
Vol 213 (4) ◽  
pp. 1145-1188 ◽  
Author(s):  
E. Jane Albert Hubbard ◽  
Tim Schedl
Keyword(s):  
Stem Cell ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Control Cell ◽  
Cell System ◽  
Germline Stem Cell ◽  
Cell Systems ◽  
Stem Cell Fate ◽  
C Elegans ◽  
Stem Cell System

Stem cell systems regulate tissue development and maintenance. The germline stem cell system is essential for animal reproduction, controlling both the timing and number of progeny through its influence on gamete production. In this review, we first draw general comparisons to stem cell systems in other organisms, and then present our current understanding of the germline stem cell system in Caenorhabditis elegans. In contrast to stereotypic somatic development and cell number stasis of adult somatic cells in C. elegans, the germline stem cell system has a variable division pattern, and the system differs between larval development, early adult peak reproduction and age-related decline. We discuss the cell and developmental biology of the stem cell system and the Notch regulated genetic network that controls the key decision between the stem cell fate and meiotic development, as it occurs under optimal laboratory conditions in adult and larval stages. We then discuss alterations of the stem cell system in response to environmental perturbations and aging. A recurring distinction is between processes that control stem cell fate and those that control cell cycle regulation. C. elegans is a powerful model for understanding germline stem cells and stem cell biology.

Cell interactions involved in development of the bilaterally symmetrical intestinal valve cells during embryogenesis in Caenorhabditis elegans

Development ◽  
1992 ◽  
Vol 116 (4) ◽  
pp. 1113-1122 ◽  
Author(s):  
B. Bowerman ◽  
F.E. Tax ◽  
J.H. Thomas ◽  
J.R. Priess
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Cell Interaction ◽  
Cell Interactions ◽  
Cell Type ◽  
Cell Stage ◽  
Development Potential ◽  
Symmetrical Pattern ◽  
A Cell ◽  
Symmetrical Cell

We describe two different cell interactions that appear to be required for the proper development of a pair of bilaterally symmetrical cells in Caenorhabditis elegans called the intestinal valve cells. Previous experiments have shown that at the beginning of the 4-cell stage of embryogenesis, two sister blastomeres called ABa and ABp are equivalent in development potential. We show that cell interactions between ABp and a neighboring 4-cell-stage blastomere called P2 distinguish the fates of ABa and ABp by inducing descendants of ABp to produce the intestinal valve cells, a cell type not made by ABa. A second cell interaction appears to occur later in embryogenesis when two bilaterally symmetrical descendants of ABp, which both have the potential to produce valve cells, contact each other; production of the valve cells subsequently becomes limited to only one of the two descendants. This second interaction does not occur properly if the two symmetrical descendants of ABp are prevented from contacting each other. Thus the development of the intestinal valve cells appears to require both an early cell interaction that establishes a bilaterally symmetrical pattern of cell fate and a later interaction that breaks the symmetrical cell fate pattern by restricting to only one of two cells the ability to produce a pair of valve cells.

The fog-3 gene and regulation of cell fate in the germ line of Caenorhabditis elegans.

Genetics ◽  
1995 ◽  
Vol 139 (2) ◽  
pp. 561-577 ◽  
Author(s):  
R E Ellis ◽  
J Kimble
Keyword(s):  
Caenorhabditis Elegans ◽  
Germ Cell ◽  
Sexual Identity ◽  
Cell Fate ◽  
Germ Cells ◽  
Regulatory Network ◽  
Germ Line ◽  
The Other ◽  
Nematode Caenorhabditis Elegans ◽  
Inhibitory Interactions

Abstract In the nematode Caenorhabditis elegans, germ cells normally adopt one of three fates: mitosis, spermatogenesis or oogenesis. We have identified and characterized the gene fog-3, which is required for germ cells to differentiate as sperm rather than as oocytes. Analysis of double mutants suggests that fog-3 is absolutely required for spermatogenesis and acts at the end of the regulatory hierarchy controlling sex determination for the germ line. By contrast, mutations in fog-3 do not alter the sexual identity of other tissues. We also have characterized the null phenotype of fog-1, another gene required for spermatogenesis; we demonstrate that it too controls the sexual identity of germ cells but not of other tissues. Finally, we have studied the interaction of these two fog genes with gld-1, a gene required for germ cells to undergo oogenesis rather than mitosis. On the basis of these results, we propose that germ-cell fate might be controlled by a set of inhibitory interactions among genes that specify one of three fates: mitosis, spermatogenesis or oogenesis. Such a regulatory network would link the adoption of one germ-cell fate to the suppression of the other two.

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.

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