scholarly journals Genetic and phenotypic studies of hypomorphic lin-12 mutants in Caenorhabditis elegans.

Genetics ◽  
1993 ◽  
Vol 135 (3) ◽  
pp. 755-763 ◽  
Author(s):  
M Sundaram ◽  
I Greenwald
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
System Development ◽  
Egg Laying ◽  
Cell Fates ◽  
Hypomorphic Allele ◽  
High Penetrance ◽  
Hypomorphic Alleles ◽  
Null Mutants

Abstract The lin-12 gene of Caenorhabditis elegans is thought to encode a receptor for intercellular signals that specify certain cell fates during development. We describe several alleles of lin-12 that reduce but do not eliminate lin-12 activity (hypomorphic alleles). These alleles cause a novel egg-laying defective (Egl) phenotype in hermaphrodites as well as incompletely penetrant cell fate transformations seen with high penetrance in lin-12 null mutants. Characterization of the Egl phenotype revealed additional roles of lin-12 in the development of the egg-laying system that were not apparent from studying lin-12 null mutants: lin-12 activity is required for proper early vulval morphogenesis as well as for some unknown later aspect of egg-laying system development. Reversion of the Egl phenotype caused by one lin-12 hypomorphic allele was used to identify potential interacting genes as described in the accompanying paper.

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.

Characterization of Caenorhabditis elegans lectin-binding mutants.

Genetics ◽  
1992 ◽  
Vol 131 (4) ◽  
pp. 867-881 ◽  
Author(s):  
C D Link ◽  
M A Silverman ◽  
M Breen ◽  
K E Watt ◽  
S A Dames
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Lectin Binding ◽  
Cellular Level ◽  
Extracellular Proteins ◽  
Egg Laying ◽  
Cell Surface Receptor ◽  
Surface Binding ◽  
Surface Receptor

Abstract We have identified 45 mutants of Caenorhabditis elegans that show ectopic surface binding of the lectins wheat germ agglutinin (WGA) and soybean agglutinin (SBA). These mutations are all recessive and define six genes: srf-2, srf-3, srf-4, srf-5, srf-8 and srf-9. Mutations in these genes fall into two phenotypic classes: srf-2, -3, -5 mutants are grossly wild-type, except for their lectin-binding phenotype; srf-4, -8, -9 mutants have a suite of defects, including uncoordinated movement, abnormal egg laying, and defective copulatory bursae morphogenesis. Characterization of these pleiotropic mutants at the cellular level reveals defects in the migration of the gonadal distal tip cell and in axon morphology. Unexpectedly, the pleiotropic mutations also interact with mutations in the lin-12 gene, which encodes a putative cell surface receptor involved in the control of cell fate. We propose that the underlying defect in the pleiotropic mutations may be in the general processing or secretion of extracellular proteins.

scholarly journals Ras is required for a limited number of cell fates and not for general proliferation in Caenorhabditis elegans.

1997 ◽  
Vol 17 (5) ◽  
pp. 2716-2722 ◽  
Author(s):  
J Yochem ◽  
M Sundaram ◽  
M Han
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Cellular Proliferation ◽  
Duct Cell ◽  
Small Gtpase ◽  
Cell Fates ◽  
Larval Stages ◽  
Culture Cells ◽  
Genetic Mosaic ◽  
Distinct Cell

Experiments with mammalian tissue culture cells have implicated the small GTPase Ras in the control of cellular proliferation. Evidence is presented here that this is not the case for a living animal, the nematode Caenorhabditis elegans: proliferation late in embryogenesis and throughout the four larval stages is not noticeably affected in animals lacking Ras in various parts of their cell lineages. Instead, genetic mosaic analysis of the let-60 gene suggests that Ras is required only, at least later in development (a maternal effect cannot be excluded), for establishment of a few temporally and spatially distinct cell fates. Only one of these, the duct cell fate, appears to be essential for viability.

brakeless is required for lamina targeting of R1-R6 axons in the Drosophila visual system

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2291-2301 ◽  
Author(s):  
K. Senti ◽  
K. Keleman ◽  
F. Eisenhaber ◽  
B.J. Dickson
Keyword(s):  
Visual System ◽  
System Development ◽  
Photoreceptor Cells ◽  
Protein Isoforms ◽  
Cell Fates ◽  
Transgenic Expression ◽  
First Optic Ganglion ◽  
Visual System Development ◽  
The Brain

Photoreceptors in the Drosophila eye project their axons retinotopically to targets in the optic lobe of the brain. The axons of photoreceptor cells R1-R6 terminate in the first optic ganglion, the lamina, while R7 and R8 axons project through the lamina to terminate in distinct layers of the second ganglion, the medulla. Here we report the identification of the gene brakeless (bks) and show that its function is required in the developing eye specifically for the lamina targeting of R1-R6 axons. In mosaic animals lacking bks function in the eye, R1-R6 axons project through the lamina to terminate in the medulla. Other aspects of visual system development appear completely normal: photoreceptor and lamina cell fates are correctly specified, R7 axons correctly target the medulla, and both correctly targeted R7 axons and mistargeted R1-R6 axons maintain their retinotopic order with respect to both anteroposterior and dorsoventral axes. bks encodes two unusually hydrophilic nuclear protein isoforms, one of which contains a putative C(2)H(2) zinc finger domain. Transgenic expression of either Bks isoform is sufficient to restore the lamina targeting of R1-R6 axons in bks mosaics, but not to retarget R7 or R8 axons to the lamina. These data demonstrate the existence of a lamina-specific targeting mechanism for R1-R6 axons in the Drosophila visual system, and provide the first entry point in the molecular characterization of this process.

scholarly journals ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System

2020 ◽  
Vol 10 (6) ◽  
pp. 1949-1962 ◽  
Author(s):  
Elyse L. Christensen ◽  
Alexandra Beasley ◽  
Jessica Radchuk ◽  
Zachery E. Mielko ◽  
Elicia Preston ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Neural Development ◽  
System Development ◽  
Neuronal Cell ◽  
Nervous System Development ◽  
Link Type ◽  
Neuroblast Migration

Proper nervous system development is required for an organism’s survival and function. Defects in neurogenesis have been linked to neurodevelopmental disorders such as schizophrenia and autism. Understanding the gene regulatory networks that orchestrate neural development, specifically cascades of proneural transcription factors, can better elucidate which genes are most important during early neurogenesis. Neurogenins are a family of deeply conserved factors shown to be both necessary and sufficient for the development of neural subtypes. However, the immediate downstream targets of neurogenin are not well characterized. The objective of this study was to further elucidate the role of ngn-1/neurogenin in nervous system development and to identify its downstream transcriptional targets, using the nematode Caenorhabditis elegans as a model for this work. We found that ngn-1 is required for axon outgrowth, nerve ring architecture, and neuronal cell fate specification. We also showed that ngn-1 may have roles in neuroblast migration and epithelial integrity during embryonic development. Using RNA sequencing and comparative transcriptome analysis, we identified eight transcription factors (hlh-34/NPAS1, unc-42/PROP1, ceh-17/PHOX2A, lim-4/LHX6, fax-1/NR2E3, lin-11/LHX1, tlp-1/ZNF503, and nhr-23/RORB) whose transcription is activated, either directly or indirectly, by ngn-1. Our results show that ngn-1 has a role in transcribing known terminal regulators that establish and maintain cell fate of differentiated neural subtypes and confirms that ngn-1 functions as a proneural transcription factor in C. elegans neurogenesis.

scholarly journals A genetic analysis of deltex and its interaction with the Notch locus in Drosophila melanogaster.

Genetics ◽  
1992 ◽  
Vol 131 (1) ◽  
pp. 99-112 ◽  
Author(s):  
M J Gorman ◽  
J R Girton
Keyword(s):  
Cell Fate ◽  
Developmental Pathways ◽  
Phenotypic Characterization ◽  
Loss Of Function ◽  
Cell Fates ◽  
Cone Cells ◽  
Notch Gene ◽  
Notch Locus ◽  
Fate Decision

Abstract During Drosophila development networks of genes control the developmental pathways that specify cell fates. The Notch gene is a well characterized member of some cell fate pathways, and several other genes belonging to these same pathways have been identified because they share a neurogenic null phenotype with Notch. However, it is unlikely that the neurogenic genes represent all of the genes in these pathways. The goal of this research was to use a genetic approach to identify and characterize one of the other genes that acts with Notch to specify cell fate. Mutant alleles of genes in the same pathway should have phenotypes similar to Notch alleles and should show phenotypic interactions with Notch alleles. With this approach we identified the deltex gene as a potential cell fate gene. An extensive phenotypic characterization of loss-of-function deltex phenotypes showed abnormalities (such as thick wing veins, double bristles and extra cone cells) that suggest that deltex is involved in cell fate decision processes. Phenotypic interactions between deltex and Notch as seen in double mutants showed that Notch and deltex do not code for duplicate functions and that the two genes function together in many different developing tissues. The results of these investigations lead to the conclusion that the deltex gene functions with the Notch gene in one or more developmental pathways to specify cell fate.

Cell cycle-dependent sequencing of cell fate decisions in Caenorhabditis elegans vulva precursor cells

Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1947-1956 ◽  
Author(s):  
V. Ambros
Keyword(s):  
Cell Cycle ◽  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Precursor Cells ◽  
S Phase ◽  
Cycle Phase ◽  
Cell Fates ◽  
Cell Fate Decisions ◽  
Cycle Arrest ◽  
Cycle Dependent

In Caenorhabditis elegans, the fates of the six multipotent vulva precursor cells (VPCs) are specified by extracellular signals. One VPC expresses the primary (1 degrees) fate in response to a Ras-mediated inductive signal from the gonad. The two VPCs flanking the 1 degrees cell each express secondary (2 degrees) fates in response to lin-12-mediated lateral signaling. The remaining three VPCs each adopt the non-vulval tertiary (3 degrees) fate. Here I describe experiments examining how the selection of these vulval fates is affected by cell cycle arrest and cell cycle-restricted lin-12 activity. The results suggest that lin-12 participates in two developmental decisions separable by cell cycle phase: lin-12 must act prior to the end of VPC S phase to influence a 1 degrees versus 2 degrees cell fate choice, but must act after VPC S phase to influence a 3 degrees versus 2 degrees cell fate choice. Coupling developmental decisions to cell cycle transitions may provide a mechanism for prioritizing or ordering choices of cell fates for multipotential cells.

scholarly journals The Caenorhabditis elegans lin-12 gene mediates induction of ventral uterine specialization by the anchor cell

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 263-271 ◽  
Author(s):  
A.P. Newman ◽  
J.G. White ◽  
P.W. Sternberg
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Lateral Inhibition ◽  
Critical Role ◽  
Egg Laying ◽  
Cell Interactions ◽  
The Other ◽  
Cell Type ◽  
Specialized Cell ◽  
Anchor Cell

The anchor cell (AC) of the Caenorhabditis elegans gonad has a critical role in the development of a functional egg-laying system, which is accomplished through cell-cell interactions. Lateral inhibitory lin-12-mediated signaling among two bipotential cells causes one to adopt the ventral uterine precursor (VU) cell fate while the other becomes the AC. The AC then induces formation of vulval tissue. We find that the AC also induces a particular ventral uterine intermediate precursor fate (pi) by a mechanism that is genetically and temporally distinct from vulval induction. This process requires lin-12, but unlike previously described lin-12-mediated decisions, signaling is unidirectional, is between dissimilar cells and does not involve lateral inhibition. The pi fates are necessary for egg laying and appear to produce a distinct specialized cell type. Thus, patterning of the ventral uterus by the AC is crucial to the development of a functional egg-laying system.

scholarly journals Alin-45 rafEnhancer Screen Identifieseor-1,eor-2and Unusual Alleles of Ras Pathway Genes inCaenorhabditis elegans

Genetics ◽  
2002 ◽  
Vol 161 (1) ◽  
pp. 121-131 ◽  
Author(s):  
Christian E Rocheleau ◽  
Robyn M Howard ◽  
Alissa P Goldman ◽  
Mandy L Volk ◽  
Laura J Girard ◽  
...  
Keyword(s):  
Cell Fate ◽  
System Development ◽  
Phosphorylation Site ◽  
Egg Laying ◽  
Excretory System ◽  
Temperature Sensitive ◽  
Ras Signaling ◽  
Multiple Alleles ◽  
Ras Pathway ◽  
Fate Specification

AbstractIn Caenorhabditis elegans, the Ras/Raf/MEK/ERK signal transduction pathway controls multiple processes including excretory system development, P12 fate specification, and vulval cell fate specification. To identify positive regulators of Ras signaling, we conducted a genetic screen for mutations that enhance the excretory system and egg-laying defects of hypomorphic lin-45 raf mutants. This screen identified unusual alleles of several known Ras pathway genes, including a mutation removing the second SH3 domain of the sem-5/Grb2 adaptor, a temperature-sensitive mutation in the helical hairpin of let-341/Sos, a gain-of-function mutation affecting a potential phosphorylation site of the lin-1 Ets domain transcription factor, a dominantnegative allele of ksr-1, and hypomorphic alleles of sur-6/PP2A-B, sur-2/Mediator, and lin-25. In addition, this screen identified multiple alleles of two newly identified genes, eor-1 and eor-2, that play a relatively weak role in vulval fate specification but positively regulate Ras signaling during excretory system development and P12 fate specification. The spectrum of identified mutations argues strongly for the specificity of the enhancer screen and for a close involvement of eor-1 and eor-2 in Ras signaling.

scholarly journals Maintenance of Cell Fates by Regulation of the Histone Variant H3.3 in Caenorhabditis elegans

2018 ◽  
Author(s):  
Yukimasa Shibata ◽  
Kiyoji Nishiwaki
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Fate ◽  
Binding Protein ◽  
Ectopic Expression ◽  
Cell Types ◽  
Histone Variants ◽  
Histone Variant ◽  
Histone H4 ◽  
Cell Fates ◽  
Selector Genes

HighlightsTLK-1 maintains cell fates by repression of selector genesTLK-1 and downstream H3 chaperone CAF1 inhibit H3.3 depositionLoss of sin-3 suppresses the defect in cell-fate maintenance of tlk-1 mutantsAcH4-binding protein BET-1 is necessary for sin-3 suppressionSummaryCell-fate maintenance is important to preserve the variety of cell types that are essential for the formation and function of tissues. We previously showed that the acetylated histone H4-binding protein BET-1 maintains cell fate by recruiting the histone variant H2A.z. Here, we report that Caenorhabditis elegans tousled-like kinase TLK-1 and the histone H3 chaperone CAF1 maintain cell fate by preventing the incorporation of histone variant H3.3 into nucleosomes, thereby repressing ectopic expression of transcription factors that induce cell-fate specification. Genetic analyses suggested that TLK-1 and BET-1 act in parallel pathways. In tlk-1 mutants, the loss of SIN-3, which promotes histone acetylation, suppressed a defect in cell-fate maintenance in a manner dependent on MYST family histone acetyltransferase MYS-2 and BET-1. sin-3 mutation also suppressed abnormal H3.3 incorporation. Thus, we propose that the regulation and interaction of histone variants play crucial roles in cell-fate maintenance through the regulation of selector genes.

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