Effect of a Neuropeptide Gene on Behavioral States in Caenorhabditis elegans Egg-Laying

Abstract Egg-laying behavior in the nematode Caenorhabditis elegans involves fluctuation between alternative behavioral states: an inactive state, during which eggs are retained in the uterus, and an active state, during which eggs are laid in bursts. We have found that the flp-1 gene, which encodes a group of structurally related neuropeptides, functions specifically to promote the switch from the inactive to the active egg-laying state. Recessive mutations in flp-1 caused a significant increase in the duration of the inactive phase, yet egg-laying within the active phase was normal. This pattern resembled that previously observed in mutants defective in the biosynthesis of serotonin, a neuromodulator implicated in induction of the active phase. Although flp-1 mutants were sensitive to stimulation of egg-laying by serotonin, the magnitude of their serotonin response was abnormally low. Thus, the flp-1-encoded peptides and serotonin function most likely function in concert to facilitate the onset of the active egg-laying phase. Interestingly, we observed that flp-1 is necessary for animals to down-regulate their rate of egg-laying in the absence of food. Because flp-1 is known to be expressed in interneurons that are postsynaptic to a variety of chemosensory cells, the FLP-1 peptides may function to regulate the activity of the egg-laying circuitry in response to sensory cues.

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ISOLATION AND GENETIC CHARACTERIZATION OF CELL-LINEAGE MUTANTS OF THE NEMATODE CAENORHABDITIS ELEGANS

Genetics ◽

10.1093/genetics/96.2.435 ◽

1980 ◽

Vol 96 (2) ◽

pp. 435-454 ◽

Cited By ~ 20

Author(s):

H Robert Horvitz ◽

John E Sulston

Keyword(s):

Caenorhabditis Elegans ◽

Cell Lineage ◽

Embryonic Cell ◽

Null Alleles ◽

Recessive Mutation ◽

Incomplete Penetrance ◽

Nematode Caenorhabditis Elegans ◽

Cell Lineages ◽

Cell Divisions ◽

Recessive Mutations

ABSTRACT Twenty-four mutants that alter the normally invariant post-embryonic cell lineages of the nematode Caenorhabditis elegans have been isolated and genetically characterized. In some of these mutants, cell divisions fail that occur in wild-type animals; in other mutants, cells divide that do not normally do so. The mutants differ in the specificities of their defects, so that it is possible to identify mutations that affect some cell lineages but not others. These mutants define 14 complementation groups, which have been mapped. The abnormal phenotype of most of the cell-lineage mutants results from a single recessive mutation; however, the excessive cell divisions characteristic of one strain, CB1322, require the presence of two unlinked recessive mutations. All 24 cell-lineage mutants display incomplete penetrance and/or variable expressivity. Three of the mutants are suppressed by pleiotropic suppressors believed to be specific for null alleles, suggesting that their phenotypes result from the complete absence of gene activity.

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Food responsiveness regulates episodic behavioral states in Caenorhabditis elegans

Journal of Neurophysiology ◽

10.1152/jn.00555.2016 ◽

2017 ◽

Vol 117 (5) ◽

pp. 1911-1934 ◽

Cited By ~ 24

Author(s):

Richard J. McCloskey ◽

Anthony D. Fouad ◽

Matthew A. Churgin ◽

Christopher Fang-Yen

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Body Movement ◽

Egg Laying ◽

The Body ◽

Hierarchical Organization ◽

Whole Body ◽

Locomotory Activity ◽

Behavioral States ◽

External Environments

Animals optimize survival and reproduction in part through control of behavioral states, which depend on an organism’s internal and external environments. In the nematode Caenorhabditis elegans a variety of behavioral states have been described, including roaming, dwelling, quiescence, and episodic swimming. These states have been considered in isolation under varied experimental conditions, making it difficult to establish a unified picture of how they are regulated. Using long-term imaging, we examined C. elegans episodic behavioral states under varied mechanical and nutritional environments. We found that animals alternate between high-activity (active) and low-activity (sedentary) episodes in any mechanical environment, while the incidence of episodes and their behavioral composition depend on food levels. During active episodes, worms primarily roam, as characterized by continuous whole body movement. During sedentary episodes, animals exhibit dwelling (slower movements confined to the anterior half of the body) and quiescence (a complete lack of movement). Roaming, dwelling, and quiescent states are manifest not only through locomotory characteristics but also in pharyngeal pumping (feeding) and in egg-laying behaviors. Next, we analyzed the genetic basis of behavioral states. We found that modulation of behavioral states depends on neuropeptides and insulin-like signaling in the nervous system. Sensory neurons and the Foraging homolog EGL-4 regulate behavior through control of active/sedentary episodes. Optogenetic stimulation of dopaminergic and serotonergic neurons induced dwelling, implicating dopamine as a dwell-promoting neurotransmitter. Our findings provide a more unified description of behavioral states and suggest that perception of nutrition is a conserved mechanism for regulating animal behavior. NEW & NOTEWORTHY One strategy by which animals adapt to their internal states and external environments is by adopting behavioral states. The roundworm Caenorhabditis elegans is an attractive model for investigating how behavioral states are genetically and neuronally controlled. Here we describe the hierarchical organization of behavioral states characterized by locomotory activity, feeding, and egg-laying. We show that decisions to engage in these behaviors are controlled by the nervous system through insulin-like signaling and the perception of food.

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Rules of Nonallelic Noncomplementation at the Synapse in Caenorhabditis elegans

Genetics ◽

10.1093/genetics/158.1.209 ◽

2001 ◽

Vol 158 (1) ◽

pp. 209-220 ◽

Cited By ~ 1

Author(s):

Karen J Yook ◽

Stephen R Proulx ◽

Erik M Jorgensen

Keyword(s):

Caenorhabditis Elegans ◽

Gene Product ◽

Genetic Interaction ◽

Synaptic Proteins ◽

Null Alleles ◽

Nematode Caenorhabditis Elegans ◽

Recessive Mutations ◽

Genes Encoding ◽

Physical Interactions ◽

Encoding Gene

Abstract Nonallelic noncomplementation occurs when recessive mutations in two different loci fail to complement one another, in other words, the double heterozygote exhibits a phenotype. We observed that mutations in the genes encoding the physically interacting synaptic proteins UNC-13 and syntaxin/UNC-64 failed to complement one another in the nematode Caenorhabditis elegans. Noncomplementation was not observed between null alleles of these genes and thus this genetic interaction does not occur with a simple decrease in dosage at the two loci. However, noncomplementation was observed if at least one gene encoded a partially functional gene product. Thus, this genetic interaction requires a poisonous gene product to sensitize the genetic background. Nonallelic noncomplementation was not limited to interacting proteins: Although the strongest effects were observed between loci encoding gene products that bind to one another, interactions were also observed between proteins that do not directly interact but are members of the same complex. We also observed noncomplementation between genes that function at distant points in the same pathway, implying that physical interactions are not required for nonallelic noncomplementation. Finally, we observed that mutations in genes that function in different processes such as neurotransmitter synthesis or synaptic development complement one another. Thus, this genetic interaction is specific for genes acting in the same pathway, that is, for genes acting in synaptic vesicle trafficking.

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

Genetics ◽

10.1093/genetics/96.1.147 ◽

1980 ◽

Vol 96 (1) ◽

pp. 147-164 ◽

Cited By ~ 7

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.

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egl-4 Acts Through a Transforming Growth Factor-β/SMAD Pathway in Caenorhabditis elegans to Regulate Multiple Neuronal Circuits in Response to Sensory Cues

Genetics ◽

10.1093/genetics/156.1.123 ◽

2000 ◽

Vol 156 (1) ◽

pp. 123-141 ◽

Cited By ~ 1

Author(s):

Susan A Daniels ◽

Michael Ailion ◽

James H Thomas ◽

Piali Sengupta

Keyword(s):

Caenorhabditis Elegans ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Egg Laying ◽

Sensory Cues ◽

C Elegans ◽

Epistasis Analysis ◽

Dauer Larva ◽

Dauer Formation ◽

Chemosensory Behavior

Abstract Sensory cues regulate several aspects of behavior and development in Caenorhabditis elegans, including entry into and exit from an alternative developmental stage called the dauer larva. Three parallel pathways, including a TGF-β-like pathway, regulate dauer formation. The mechanisms by which the activities of these pathways are regulated by sensory signals are largely unknown. The gene egl-4 was initially identified based on its egg-laying defects. We show here that egl-4 has many pleiotropies, including defects in chemosensory behavior, body size, synaptic transmission, and dauer formation. Our results are consistent with a role for egl-4 in relaying sensory cues to multiple behavioral and developmental circuits in C. elegans. By epistasis analysis, we also place egl-4 in the TGF-β-like branch and show that a SMAD gene functions downstream of egl-4 in multiple egl-4-regulated pathways, including chemosensation.

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Three Mutants That Extend Both Mean and Maximum Life Span of the Nematode, Caenorhabditis elegans , Define the age-1 Gene

Science of Aging Knowledge Environment ◽

10.1126/sageke.2002.38.cp23 ◽

2002 ◽

Vol 2002 (38) ◽

Author(s):

David B. Friedman ◽

Thomas E. Johnson

Keyword(s):

Caenorhabditis Elegans ◽

Life Span ◽

Pleiotropic Effect ◽

Wild Type ◽

Nematode Caenorhabditis Elegans ◽

Maximum Life Span ◽

Gerontological Society ◽

Recessive Mutations ◽

Mutant Strains ◽

Independent Mutation

Long-lived mutants in the nematode Caenorhabditis elegans have been studied to determine if the mutations responsible for extended life were allelic. Three of four mutant strains studied (MK31, MK542, MK546) contain recessive mutations that significantly lengthen life; MK542 and MK546 consistently fail to complement the long life phenotype of age-1 and are therefore allelic. MK31, although longer lived than wild type, is equivocal, in some cases failing to complement age-1 but not in others. All three long-lived strains have reduced hermaphrodite self-fertility and also fail to complement for this presumed pleiotropic effect of the age-1 mutation. Each of these three strains also contains an independent mutation at unc-31 IV. Since the mutants were isolated in the same mutant hunt (Klass, 1983) using protocols that did not guarantee independence, the mutations cannot be assumed to be independently isolated. Copyright (c) The Gerontological Society of America. Reproduced by permission of the publisher. David B. Friedman, Thomas E. Johnson, Three Mutants That Extend Both Mean and Maximum Life Span of the Nematode, Caenorhabditis elegans , Define the age-1 Gene. J. Gerontol. 43 , B102-B109 (1988).

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Cell interactions control the direction of outgrowth, branching and fasciculation of the HSN axons of Caenorhabditis elegans

Development ◽

10.1242/dev.117.3.1071 ◽

1993 ◽

Vol 117 (3) ◽

pp. 1071-1087 ◽

Cited By ~ 17

Author(s):

G. Garriga ◽

C. Desai ◽

H.R. Horvitz

Keyword(s):

Caenorhabditis Elegans ◽

Epithelial Cells ◽

Motor Neurons ◽

Growth Cone ◽

Nerve Cord ◽

Ventral Nerve Cord ◽

Egg Laying ◽

Axonal Guidance ◽

Nematode Caenorhabditis Elegans ◽

Vulval Precursor Cells

The two serotonergic HSN motor neurons of the nematode Caenorhabditis elegans innervate the vulval muscles and stimulate egg laying by hermaphrodites. By analyzing mutant and laser-operated animals, we find that both epithelial cells of the developing vulva and axons of the ventral nerve cord are required for HSN axonal guidance. Vulval precursor cells help guide the growth cone of the emerging HSN axon to the ventral nerve cord. Vulval cells also cause the two HSN axons to join the ventral nerve cord in two separate fascicles and to defasciculate from the ventral nerve cord and branch at the vulva. The axons of either the PVP or PVQ neurons are also necessary for the HSN axons to run in two separate fascicles within the ventral nerve cord. Our observations indicate that the outgrowth of the HSN axon is controlled in multiple ways by both neuronal and nonneuronal cells.

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Optogenetic analyses of neuronal network function and synaptic transmission in Caenorhabditis elegans

e-Neuroforum ◽

10.1515/s13295-014-0064-6 ◽

2014 ◽

Vol 20 (4) ◽

Author(s):

A. Gottschalk

Keyword(s):

Caenorhabditis Elegans ◽

Optical Sensors ◽

Behavioral Change ◽

Nematode Caenorhabditis Elegans ◽

Ideal Model ◽

Network Function ◽

Primary Signal ◽

Ideal Model System ◽

Chemical Synapses ◽

Stimulation Of

AbstractThe transparent nematode Caenorhabditis elegans, with its anatomically well-defined nervous system comprising 302 neurons that regulate quantifiable behaviors, is an ideal model system for the development and application of optogenetic methods. Optogenetically modified neurons can be acutely excited or inhibited by light and the effects on a distinct behavior observed. Special lighting systems allow the manipulation of several nerve cells that act as “nodes” of small neural circuits, with different colors of light, so as to control different optogenetic tools independently and simultaneously. In addition, genetically encoded optical sensors for neuronal activity make it possible to draw conclusions even when the optogenetic intervention causes no obvious behavioral change. The stimulation of quantifiable behaviors permits the analysis of the function of genes necessary in the corresponding neuron for the encoding or amplification of the primary signal. Finally, following optogenetic stimulation, the function of chemical synapses and their proteins can also be analyzed by electrophysiology or electron microscopy.

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Genes Affecting the Activity of Nicotinic Receptors Involved in Caenorhabditis elegans Egg-Laying Behavior

Genetics ◽

10.1093/genetics/157.4.1599 ◽

2001 ◽

Vol 157 (4) ◽

pp. 1599-1610

Author(s):

Jinah Kim ◽

Daniel S Poole ◽

Laura E Waggoner ◽

Anthony Kempf ◽

David S Ramirez ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Nicotinic Acetylcholine Receptors ◽

Nicotinic Receptor ◽

Molecular Basis ◽

Acetylcholine Receptors ◽

Nicotinic Receptors ◽

Receptor Gene ◽

Egg Laying ◽

Cholinergic Neurotransmission ◽

Stimulation Of

Abstract Egg-laying behavior in Caenorhabditis elegans is regulated by multiple neurotransmitters, including acetylcholine and serotonin. Agonists of nicotinic acetylcholine receptors such as nicotine and levamisole stimulate egg laying; however, the genetic and molecular basis for cholinergic neurotransmission in the egg-laying circuitry is not well understood. Here we describe the egg-laying phenotypes of eight levamisole resistance genes, which affect the activity of levamisole-sensitive nicotinic receptors in nematodes. Seven of these genes, including the nicotinic receptor subunit genes unc-29, unc-38, and lev-1, were essential for the stimulation of egg laying by levamisole, though they had only subtle effects on egg-laying behavior in the absence of drug. Thus, these genes appear to encode components of a nicotinic receptor that can promote egg laying but is not necessary for egg-laying muscle contraction. Since the levamisole-receptor mutants responded to other cholinergic drugs, other acetylcholine receptors are likely to function in parallel with the levamisole-sensitive receptors to mediate cholinergic neurotransmission in the egg-laying circuitry. In addition, since expression of functional unc-29 in muscle cells restored levamisole sensitivity under some but not all conditions, both neuronal and muscle cell UNC-29 receptors are likely to contribute to the regulation of egg-laying behavior. Mutations in one levamisole receptor gene, unc-38, also conferred both hypersensitivity and reduced peak response to serotonin; thus nicotinic receptors may play a role in regulating serotonin response pathways in the egg-laying neuromusculature.

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Comparative genomic analysis of the human and nematode Caenorhabditis elegans uncovers potential reproductive genes and disease associations in humans

Physiological Genomics ◽

10.1152/physiolgenomics.00063.2018 ◽

2018 ◽

Vol 50 (11) ◽

pp. 1002-1014 ◽

Cited By ~ 1

Author(s):

Yongsoon Kim ◽

YoungJoon Park ◽

JoonYeon Hwang ◽

KyuBum Kwack

Keyword(s):

Caenorhabditis Elegans ◽

Egg Laying ◽

Nuclear Bodies ◽

Human Reproduction ◽

Mechanistic Study ◽

Comparative Genomic ◽

Nematode Caenorhabditis Elegans ◽

C Elegans ◽

Reproductive Genes ◽

Disease Associations

Reproduction is an important biological process. However, studies of human reproduction at the molecular level are limited due to the difficulty of performing in vivo studies. Hence, a mechanistic understanding of human reproduction remains still poor. Thus, it is important to use an alternative model organism for mechanistic studies of human reproduction. In this study, we used the nematode Caenorhabditis elegans as a model for studying human reproduction and identified 61 human and 535 worm reproductive genes through a combination of comparative genomic and Gene Ontology (GO) analyses. Interestingly, in terms of sex specificity, the number of male-specific genes was greater than the number of female-specific genes. Gene enrichment analysis identified biologically significant processes such as protein localization to cajal bodies/telomeres/nuclear bodies/chromosomes, helicase activity, pyrimidine biosynthesis, and determination of adult lifespan. Regarding the analysis of human reproductive diseases among the identified genes, 10 and 12 genes were identified in the human- and C. elegans-based analyses, respectively. In addition, RNA interference knockdown of a newly identified F52H2.6/DHCR24 gene increased brood size and ovulation/egg-laying rate in C. elegans. Therefore, gene identification, disease associations, and a proof-of-concept experiment using C. elegans will not only provide insights into mechanistic study of human reproduction, but also demonstrate the utility in studying human reproduction.

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