scholarly journals Homeostatic feedback modulates the development of two-state patterned activity in a model serotonin motor circuit in Caenorhabditis elegans

2017 ◽  
Author(s):  
Bhavya Ravi ◽  
Jessica Garcia ◽  
Kevin M. Collins
Keyword(s):  
Caenorhabditis Elegans ◽  
Muscle Activity ◽  
Egg Laying ◽  
Burst Firing ◽  
Neuron Activity ◽  
Motor Circuit ◽  
Adult Behavior ◽  
C Elegans ◽  
Vulval Muscle ◽  
Circuit Development

AbstractNeuron activity accompanies synapse formation and maintenance, but how early circuit activity contributes to behavior development is not well understood. Here, we use the Caenorhabditis elegans egg-laying motor circuit as a model to understand how coordinated cell and circuit activity develops and drives a robust two-state behavior in adults. Using calcium imaging in behaving animals, we find the serotonergic Hermaphrodite Specific Neurons (HSNs) and vulval muscles show rhythmic calcium transients in L4 larvae before eggs are produced. HSN activity in L4 is tonic and lacks the alternating burst-firing/quiescent pattern seen in egg-laying adults. Vulval muscle activity in L4 is initially uncoordinated but becomes synchronous as the anterior and posterior muscle arms meet at HSN synaptic release sites. However, coordinated muscle activity does not require presynaptic HSN input. Using reversible silencing experiments, we show that neuronal and vulval muscle activity in L4 is not required for the onset of adult behavior. Instead, the accumulation of eggs in the adult uterus renders the muscles sensitive to HSN input. Sterilization or acute electrical silencing of the vulval muscles inhibits presynaptic HSN activity, and reversal of muscle silencing triggers a homeostatic increase in HSN activity and egg release that maintains ~12-15 eggs in the uterus. Feedback of egg accumulation depends upon the vulval muscle postsynaptic terminus, suggesting a retrograde signal sustains HSN synaptic activity and egg release. Our results show that egg-laying behavior in C. elegans is driven by a homeostat that scales serotonin motor neuron activity in response to postsynaptic muscle feedback.Significance StatementThe functional importance of early, spontaneous neuron activity in synapse and circuit development is not well understood. Here we show that in the nematode C. elegans, the serotonergic Hermaphrodite Specific Neurons (HSNs) and postsynaptic vulval muscles show activity during circuit development, well before the onset of adult behavior. Surprisingly, early activity is not required for circuit development or the onset of adult behavior, and the circuit remains unable to drive egg laying until fertilized embryos are deposited into the uterus. Egg accumulation potentiates vulval muscle excitability, but ultimately acts to promote burst firing in the presynaptic HSNs during which eggs are laid. Our results suggest that mechanosensory feedback acts at three distinct steps to initiate, sustain, and terminate C. elegans egg-laying circuit activity and behavior.

Muscle and nerve-specific regulation of a novel NK-2 class homeodomain factor in Caenorhabditis elegans

Development ◽  
1998 ◽  
Vol 125 (3) ◽  
pp. 421-429 ◽  
Author(s):  
B.D. Harfe ◽  
A. Fire
Keyword(s):  
Caenorhabditis Elegans ◽  
Motor Neurons ◽  
Homeobox Gene ◽  
Cell Types ◽  
Egg Laying ◽  
Cis Acting ◽  
C Elegans ◽  
E Box ◽  
Vulval Muscle ◽  
Specific Regulation

We have identified a new Caenorhabditis elegans NK-2 class homeobox gene, designated ceh-24. Distinct cis-acting elements generate a complex neuronal and mesodermal expression pattern. A promoter-proximal enhancer mediates expression in a single pharyngeal muscle, the donut-shaped m8 cell at the posterior end of the pharynx. A second mesodermal enhancer is active in a set of eight nonstriated vulval muscles used in egg laying. Activation in the egg laying muscles requires an ‘NdE-box’ consensus motif (CATATG) which is related to, but distinct from, the standard E-box motif bound by the MyoD family of transcriptional activators. Ectodermal expression of ceh-24 is limited to a subset of sublateral motor neurons in the head of the animal; this activity requires a cis-acting activator element that is distinct from the control elements for pharyngeal and vulval muscle expression. Activation of ceh-24 in each of the three cell types coincides with the onset of differentiation. Using a set of transposon-induced null mutations, we show that ceh-24 is not essential for the formation of any of these cells. Although ceh-24 mutants have no evident defects under laboratory conditions, the pattern of ceh-24 activity is apparently important for Rhabditid nematodes: the related species C. briggsae contains a close homologue of C. elegans ceh-24 including a highly conserved and functionally equivalent set of cis-acting control signals.

scholarly journals Screening for Presenilin Inhibitors Using the Free-Living Nematode, Caenorhabditis elegans

2004 ◽  
Vol 9 (2) ◽  
pp. 147-152 ◽  
Author(s):  
Brenda R. Ellerbrock ◽  
Eileen M. Coscarelli ◽  
Mark E. Gurney ◽  
Timothy G. Geary
Keyword(s):  
Caenorhabditis Elegans ◽  
High Throughput Screening ◽  
Screening Method ◽  
Genetic System ◽  
Body Cavity ◽  
Egg Laying ◽  
The Body ◽  
Loss Of Function ◽  
C Elegans ◽  
Automated Method

Caenorhabditis elegans contains 3 homologs of presenilin genes that are associated with Alzheimer s disease. Loss-of-function mutations in C. elegans genes cause a defect in egg laying. In humans, loss of presenilin-1 (PS1) function reduces amyloid-beta peptide processing from the amyloid protein precursor. Worms were screened for compounds that block egg laying, phenocopying presenilin loss of function. To accommodate even relatively high throughput screening, a semi-automated method to quantify egg laying was devised by measuring the chitinase released into the culture medium. Chitinase is released by hatching eggs, but little is shed into the medium from the body cavity of a hermaphrodite with an egg laying deficient ( egl) phenotype. Assay validation involved measuring chitinase release from wild-type C. elegans (N2 strain), sel-12 presenilin loss-of-function mutants, and 2 strains of C. elegans with mutations in the egl-36K+ channel gene. Failure to find specific presenilin inhibitors in this collection likely reflects the small number of compounds tested, rather than a flaw in screening strategy. Absent defined biochemical pathways for presenilin, this screening method, which takes advantage of the genetic system available in C. elegans and its historical use for anthelminthic screening, permits an entry into mechanism-based discovery of drugs for Alzheimer s disease. ( Journal of Biomolecular Screening 2004:147-152)

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 RSU-1 Maintains Integrity of Caenorhabditis elegans Vulval Muscles by Regulating α-Actinin

2020 ◽  
Vol 10 (7) ◽  
pp. 2507-2517
Author(s):  
Xinyan Wang ◽  
Shuai Huang ◽  
Cunni Zheng ◽  
Wei Ge ◽  
Chuanyue Wu ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Molecular Mechanisms ◽  
Genetic Interaction ◽  
Body Movement ◽  
Egg Laying ◽  
Shape Distortion ◽  
Actin Bundle ◽  
Actin Bundles ◽  
Link Type ◽  
Vulval Muscle

Egg-laying behavior in Caenorhabditis elegans is a well-known model for investigating fundamental cellular processes. In egg-laying, muscle contraction is the relaxation of the vulval muscle to extrude eggs from the vulva. Unlike skeletal muscle, vulval muscle lacks visible striations of the sarcomere. Therefore, vulval muscle must counteract the mechanical stress, caused by egg extrusion and body movement, from inducing cell-shape distortion by maintaining its cytoskeletal integrity. However, the underlying mechanisms that regulate the cellular integrity in vulval muscles remain unclear. Here, we demonstrate that C. elegans egg-laying requires proper vulval muscle 1 (vm1), in which the actin bundle organization of vm1 muscles is regulated by Ras suppressor protein 1 (RSU-1). In the loss of RSU-1, as well as RasLET-60 overactivation, blister-like membrane protrusions and disorganized actin bundles were observed in the vm1 muscles. Moreover, RasLET-60 depletion diminished the defected actin-bundles in rsu-1 mutant. These results reveal the genetic interaction of RSU-1 and RasLET-60in vivo. In addition, our results further demonstrated that the fifth to seventh leucine-rich region of RSU-1 is required to promote actin-bundling protein, α-actinin, for actin bundle stabilization in the vm1 muscles. This expands our understanding of the molecular mechanisms of actin bundle organization in a specialized smooth muscle.

scholarly journals Distributed Rhythm Generators Underlie Caenorhabditis elegans Forward Locomotion

2017 ◽  
Author(s):  
Anthony D. Fouad ◽  
Shelly Teng ◽  
Julian R. Mark ◽  
Alice Liu ◽  
Pilar Alvarez-Illera ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Motor Neurons ◽  
Animal Behavior ◽  
Rhythm Generation ◽  
Rhythmic Movements ◽  
Neural Oscillators ◽  
Motor Circuit ◽  
C Elegans ◽  
Body Regions ◽  
Forward Locomotion

ABSTRACTCoordinated rhythmic movements are ubiquitous in animal behavior. In many organisms, chains of neural oscillators underlie the generation of these rhythms. In C. elegans, locomotor wave generation has been poorly understood; in particular, it is unclear where in the circuit rhythms are generated, and whether there exists more than one such generator. We used optogenetic and ablation experiments to probe the nature of rhythm generation in the locomotor circuit. We found that multiple sections of forward locomotor circuitry are capable of independently generating rhythms. By perturbing different components of the motor circuit, we localize the source of secondary rhythms to cholinergic motor neurons in the midbody. Using rhythmic optogenetic perturbation we demonstrate bidirectional entrainment of oscillations between different body regions. These results show that, as in many other vertebrates and invertebrates, the C. elegans motor circuit contains multiple oscillators that coordinate activity to generate behavior.

scholarly journals NEUROPHYSIOLOGICAL AND BEHAVIOURAL PERTURBATIONS IN Caenorhabditis elegans EXPOSED TO ORGANOPHOSPHATE PESTICIDES

2021 ◽  
Vol 9 (3) ◽  
pp. 343-352
Author(s):  
Rajul Jain ◽  
◽  
Priyanka Gautam ◽  
Keyword(s):  
Caenorhabditis Elegans ◽  
Fluorescent Protein ◽  
Developmental Toxicity ◽  
Yellow Fluorescent Protein ◽  
Model Organism ◽  
Egg Laying ◽  
High Exposure ◽  
C Elegans ◽  
Significant Difference ◽  
Green Fluorescent

The ubiquitous use of pesticides all over the world leads to adverse effects on both targets as well as non-target species. The extensive and uncontrolled use of organophosphates (OPs), a large group of pesticidal compounds in agricultural and household products are resulting in high exposure to humans. This research has been carried out to study the adverse effect of OPs i.e., chlorpyrifos, trichlorfon, and disulfoton on model organism Caenorhabditis elegans to evaluate their behavioural as well as developmental toxicity at different time intervals i.e., 4, 24, 48, and 72 hours (hrs) of exposure. A significant difference was observed in all the behavioural endpoints like locomotion, egg-laying, offspring count, and learning along with developmental parameters like mortality, paralysis, and growth rendering from moderate to high toxic effects. Based on the above screening, trichlorfon resulted in glutamatergic and cholinergic neurodegeneration along with elevated autofluorescence. Loss in Yellow fluorescent Protein (YFP) and Green Fluorescent Protein (GFP) was recorded by 57.96% and 30.52% using transgenic strains OH11124 (otIs388 [eat-4(fosmid)::SL2::YFP::H2B + (pBX)pha-1(+)] III) and OH13083 (otIs576 [unc-17(fosmid)::GFP + lin-44::YFP]). These results have shown the biological potency of toxicants in C. elegans and pave the way forward to provide insight into various neurogenerative diseases in humans.

scholarly journals Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans development, muscle function, and mitosis

2012 ◽  
Vol 23 (4) ◽  
pp. 543-552 ◽  
Author(s):  
Rachel Barkan ◽  
Adam J. Zahand ◽  
Kfir Sharabi ◽  
Ayelet T. Lamm ◽  
Naomi Feinstein ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Caenorhabditis Elegans ◽  
Life Span ◽  
Muscle Activity ◽  
Striated Muscle ◽  
Null Alleles ◽  
Cell Nuclei ◽  
C Elegans ◽  
Dividing Cells ◽  
Mesodermal Lineage

Emerin and LEM2 are ubiquitous inner nuclear membrane proteins conserved from humans to Caenorhabditis elegans. Loss of human emerin causes Emery-Dreifuss muscular dystrophy (EDMD). To test the roles of emerin and LEM2 in somatic cells, we used null alleles of both genes to generate C. elegans animals that were either hypomorphic (LEM-2–null and heterozygous for Ce-emerin) or null for both proteins. Single-null and hypomorphic animals were viable and fertile. Double-null animals used the maternal pool of Ce-emerin to develop to the larval L2 stage, then arrested. Nondividing somatic cell nuclei appeared normal, whereas dividing cells had abnormal nuclear envelope and chromatin organization and severe defects in postembryonic cell divisions, including the mesodermal lineage. Life span was unaffected by loss of Ce-emerin alone but was significantly reduced in LEM-2–null animals, and double-null animals had an even shorter life span. In addition to striated muscle defects, double-null animals and LEM-2–null animals showed unexpected defects in smooth muscle activity. These findings implicate human LEM2 mutations as a potential cause of EDMD and further suggest human LEM2 mutations might cause distinct disorders of greater severity, since C. elegans lacking only LEM-2 had significantly reduced life span and smooth muscle activity.

EGL-17(FGF) expression coordinates the attraction of the migrating sex myoblasts with vulval induction in C. elegans

Development ◽  
1998 ◽  
Vol 125 (6) ◽  
pp. 1083-1093 ◽  
Author(s):  
R.D. Burdine ◽  
C.S. Branda ◽  
M.J. Stern
Keyword(s):  
Caenorhabditis Elegans ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Egg Laying ◽  
Fibroblast Growth ◽  
Fgf Receptor ◽  
Precise Positioning ◽  
C Elegans ◽  
Guidance Cue ◽  
Sex Myoblasts

During the development of the egg-laying system in Caenorhabditis elegans hermaphrodites, central gonadal cells organize the alignment of the vulva with the sex myoblasts, the progenitors of the egg-laying muscles. A fibroblast growth factor [EGL-17(FGF)] and an FGF receptor [EGL-15(FGFR)] are involved in the gonadal signals that guide the migrations of the sex myoblasts. Here we show that EGL-17(FGF) can act as an instructive guidance cue to direct the sex myoblasts to their final destinations. We find that egl-17 reporter constructs are expressed in the primary vulval cell and that EGL-17(FGF) expression in this cell correlates with the precise positioning of the sex myoblasts. We postulate that EGL-17(FGF) helps to coordinate the development of a functional egg-laying system, linking vulval induction with proper sex myoblast migration.

scholarly journals Association with Soil Bacteria Enhances p38-Dependent Infection Resistance in Caenorhabditis elegans

2012 ◽  
Vol 81 (2) ◽  
pp. 514-520 ◽  
Author(s):  
Sirena Montalvo-Katz ◽  
Hao Huang ◽  
Michael David Appel ◽  
Maureen Berg ◽  
Michael Shapira
Keyword(s):  
Caenorhabditis Elegans ◽  
Mapk Pathway ◽  
16S Rrna Gene Sequencing ◽  
Egg Laying ◽  
Rrna Gene ◽  
Content Type ◽  
Immune Genes ◽  
C Elegans ◽  
Enhanced Resistance ◽  
Infection Resistance

ABSTRACTThe importance of our inner microbial communities for proper immune responses against invading pathogens is now well accepted, but the mechanisms underlying this protection are largely unknown. In this study, we usedCaenorhabditis elegansto investigate such mechanisms. Since very little is known about the microbes interacting withC. elegansin its natural environment, we began by taking the first steps to characterize theC. elegansmicrobiota. We established a natural-like environment in which initially germfree, wild-type larvae were grown on enriched soil. Bacterial members of the adultC. elegansmicrobiota were isolated by culture and identified using 16S rRNA gene sequencing. Using pure cultures of bacterial isolates as food, we identified two,Bacillus megateriumandPseudomonas mendocina, that enhanced resistance to a subsequent infection with the Gram-negative pathogenPseudomonas aeruginosa. Whereas protection byB. megateriumwas linked to impaired egg laying, corresponding to a known trade-off between fecundity and resistance, the mechanism underlying protection conferred byP. mendocinadepended on weak induction of immune genes regulated by the p38 MAPK pathway. Disruption of the p38 ortholog,pmk-1, abolished protection.P. mendocinaenhanced resistance toP. aeruginosabut not to the Gram-positive pathogenEnterococcus faecalis. Furthermore, protection fromP. aeruginosawas similarly induced by aP. aeruginosagacAmutant with attenuated virulence but not by a differentC. elegans-associatedPseudomonassp. isolate. Our results support a pivotal role for the conserved p38 pathway in microbiota-initiated immune protection and suggest that similarity between microbiota members and pathogens may play a role in such protection.

scholarly journals 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 ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 123-141 ◽  
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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