To see the other types of publications on this topic, follow the link: Nervous system Caenorhabditis elegans.
Dissertations / Theses on the topic 'Nervous system Caenorhabditis elegans'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Nervous system Caenorhabditis elegans.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Livingstone, David. "Studies on the unc-31 gene of Caenorhabditis elegans." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240106.
Full text
2
Lee, Yuk Wa. "Characterization of Mab21l2 in neural development of vertebrate model /." View abstract or full-text, 2005. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202005%20LEEY.
Full text
3
Bentley, Barry. "Connectomics of extrasynaptic signalling : applications to the nervous system of Caenorhabditis elegans." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/270033.
Full textAbstract:
Connectomics – the study of neural connectivity – is primarily concerned with the mapping and characterisation of wired synaptic links; however, it is well established that long-distance chemical signalling via extrasynaptic volume transmission is also critical to brain function. As these interactions are not visible in the physical structure of the nervous system, current approaches to connectomics are unable to capture them. This work addresses the problem of missing extrasynaptic interactions by demonstrating for the first time that whole-animal volume transmission networks can be mapped from gene expression and ligand-receptor interaction data, and analysed as part of the connectome. Complete networks are presented for the monoamine systems of Caenorhabditis elegans, along with a representative sample of selected neuropeptide systems. A network analysis of the synaptic (wired) and extrasynaptic (wireless) connectomes is presented which reveals complex topological properties, including extrasynaptic rich-club organisation with interconnected hubs distinct from those in the synaptic and gap junction networks, and highly significant multilink motifs pinpointing locations in the network where aminergic and neuropeptide signalling is likely to modulate synaptic activity. Thus, the neuronal connectome can be modelled as a multiplex network with synaptic, gap junction, and neuromodulatory layers representing inter-neuronal interactions with different dynamics and polarity. This represents a prototype for understanding how extrasynaptic signalling can be integrated into connectomics research, and provides a novel dataset for the development of multilayer network algorithms.
4
Durbin, R. M. "Studies on the development and organisation of the nervous system of Caenorhabditis elegans." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233920.
Full textAbstract:
The nematode <i>Caenorhabditis elegans</i> is a small invertebrate whose nervous system, general anatomy, and normal development are all (comparatively) extremely simple and reproducible, and have all been well characterised. This dissertation describes work based on two different approaches to the study of the control of neural development in <i>C. elgans</i>. In the first part the course of neural outgrowth in the region of the ventral nerve cord was followed from electron microscope reconstructions of a series of fixed embryos. Following this, neurons whose processes grew out early were removed by laser ablation of their parent cells and the effect on subsequent nerve outgrowth was assayed by electron microscope reconstruction. The first process to grow along the ventral cord is that of AVG, and its presence is required for the normal, highly asymmetrical structure of the cord. Two more examples of dependency on particular nerve processes for correct guidance can be deduced from experiments in which cells at the back of the animal were removed. The observations of normal development and the ablation experiments can in some cases be related to defects seen in <i>uncoordinated</i> mutants with defective nerve process organisation. The second approach was to establish and analyse a computer data base containing all the synaptic connectivity data obtained by White et al. (1986), who reconstructed at an electron microscope level the entire central nervous system regions of two <i>C. elegans</i> specimens. Since the circuitry is highly reproducible, comparisons of connections between equivalent pairs of cells can be used to infer properties of synapse formation. Overall, the <i>C. elegans</i> circuitry is anatomically highly directional, and what little chemical synaptic feedback that is seen is mostly part of reciprocal synaptic connections. There is also evidence for physical organisation of the nerve processes in subbundles of the main process tract in the central nervous system.
5
Stovall, Elizabeth L. "Analysis of mig-10, a gene involved in nervous system development in caenorhabditis elegans." Link to electronic thesis, 2004. http://www.wpi.edu/Pubs/ETD/Available/etd-0430104-142249/.
Full text
6
Burket, Christopher T. "Two genes, dig-1 and mig-10, involved in nervous system development in C. elegans." Link to electronic thesis, 2002. http://www.wpi.edu/Pubs/ETD/Available/etd-1115102-141010.
Full text
7
Ficociello, Laura Faraco. "Neuronal migration -- investigating interactions of the cytoplasmic adaptor pProtein MIG-10 in C. elegans." Worcester, Mass. : Worcester Polytechnic Institute, 2008. http://www.wpi.edu/Pubs/ETD/Available/etd-010908-103637/.
Full text
8
Birnby, Deborah Ann. "Analysis of daf-11, a transmembrane guanylyl cyclase that mediates chemosensory transduction in C. elegans /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/10300.
Full text
9
Ooi, Felicia Kye-Lyn. "Uncovering how the nervous system controls the cellular stress response in the metazoan Caenorhabditis elegans." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6236.
Full textAbstract:
The ability to accurately predict danger and implement appropriate protective responses is critical for survival. Environmental fluctuations can cause damage at the cellular level, leading to the misfolding and aggregation of proteins. Such damage is toxic to cells: in age-related neurodegenerative diseases like ALS, Parkinson’s, Alzheimer’s and Huntington’s Diseases, the accumulation of damaged proteins in the brain ultimately leads to neuronal cell death and disease onset. To date, there is still no cure to combat the progressive degeneration and cell death seen in the brains of patients. Cells within an animal possess defense programs to minimize protein damage. One such defense mechanism is the activation of a program called the Heat Shock Response, which increases production of protective proteins known as heat shock proteins (HSPs). These HSPs act as molecular chaperones to assist with the clearing out of damaged proteins. This program is implemented by a conserved transcription factor, Heat Shock Factor 1 (HSF-1). However, in brains of patients with degenerative diseases, this protective mechanism, for reasons yet unknown, is not constantly activated.
My thesis has involved the discovery of innate mechanisms that exist in organisms to activate this cellular protective mechanism against protein misfolding. My research, using the model organism Caenorhabditis elegans, has shown that the protective heat shock response in the cells of the animal can be triggered through neurohormonal signaling. The neurohormonal signaling that I am studying is one that is highly conserved across all organisms from plants to insects to mammals – serotonergic signaling. The stimulation of serotonergic signaling appears sufficient to activate the Heat Shock Response, even in the absence of real damage. In fact, the neuronal release of serotonin facilitates a pre-emptive upregulation of protective genes in the animal, which we have observed to be able to reduce the accumulation of damaged proteins in a C. elegans model of Huntington’s Disease. Additionally, I have seen that anticipating danger can enhance the animal’s stress response in a serotonin-dependent manner, thus facilitating better survival against a subsequent insult that can cause protein damage.
Together, these studies present the novel possibility of protection against neurodegenerative disease via modulation of neurotransmission and/or neurosecretion. They also allow for understanding how sensory inputs are coupled to gene expression under stressful conditions. I hope to understand the mechanism by which animals adapt to changes in their environment by coordinating their sensory input with changes in behavior and gene expression.
10
Hoskins, Roger Allen. "Molecular and genetic studies on the unc-30 and unc-31 genes of Caenorhabditis elegans." Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334107.
Full text
11
Lau, Tze Chin. "In vitro and in vivo analyses of the impact of Mab21l2 and its targets on neural patterning and differentiation in vertebrates /." View abstract or full-text, 2010. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202010%20LAU.
Full text
12
Khandekar, Anagha. "Age-related Changes in the Neuronal Architecture of Caenorhabditis Elegans: A Dissertation." eScholarship@UMMS, 2010. http://escholarship.umassmed.edu/gsbs_diss/798.
Full textAbstract:
Though symptoms such as loss of vision, decline in cognition and memory are evident during aging, the underlying processes that affect neuronal function during aging are not well understood. Unlike changes in other tissues and organs, age-related changes in the nervous system affect the overall physical, mental as well as social state of human beings. To start elucidating the molecular mechanisms underlying normal age-dependent brain decline, we have characterized structural neuronal changes occurring during Caenorhabditis elegans aging. Our analysis reveals distinct neuronal alterations that arise with age and that the types of changes and their age of onset are neuronal-type specific, highlighting the differential susceptibility of neurons to the stresses of life. We also find that these age-dependent neuronal changes are largely uncoupled from lifespan. As a first step towards understanding the neuropathological conditions manifested during senescence, we have characterized the role of the neuronal maintenance gene sax-7/L1CAM in normal C. elegans aging. Our comparison of age-related structural changes in the wild-type nervous system with that of sax-7 mutants, indicates that loss of function of sax-7 results in accelerated neuronal deterioration that mimics alterations occurring during normal aging. Conversely, overexpressing wild-type copies of SAX-7 delays some of the neuronal changes that accompany normal aging, indicating that SAX-7 plays a neuroprotective role. Additionally we find that x mechanical stress from body movements impacts the neuronal changes during adulthood. Taken together, our results give an entry point into the mechanisms of age-related neuroanatomical changes and neuronal protection.
13
Khandekar, Anagha. "Age-related Changes in the Neuronal Architecture of Caenorhabditis Elegans: A Dissertation." eScholarship@UMMS, 2015. https://escholarship.umassmed.edu/gsbs_diss/798.
Full textAbstract:
Though symptoms such as loss of vision, decline in cognition and memory are evident during aging, the underlying processes that affect neuronal function during aging are not well understood. Unlike changes in other tissues and organs, age-related changes in the nervous system affect the overall physical, mental as well as social state of human beings. To start elucidating the molecular mechanisms underlying normal age-dependent brain decline, we have characterized structural neuronal changes occurring during Caenorhabditis elegans aging. Our analysis reveals distinct neuronal alterations that arise with age and that the types of changes and their age of onset are neuronal-type specific, highlighting the differential susceptibility of neurons to the stresses of life. We also find that these age-dependent neuronal changes are largely uncoupled from lifespan. As a first step towards understanding the neuropathological conditions manifested during senescence, we have characterized the role of the neuronal maintenance gene sax-7/L1CAM in normal C. elegans aging. Our comparison of age-related structural changes in the wild-type nervous system with that of sax-7 mutants, indicates that loss of function of sax-7 results in accelerated neuronal deterioration that mimics alterations occurring during normal aging. Conversely, overexpressing wild-type copies of SAX-7 delays some of the neuronal changes that accompany normal aging, indicating that SAX-7 plays a neuroprotective role. Additionally we find that x mechanical stress from body movements impacts the neuronal changes during adulthood. Taken together, our results give an entry point into the mechanisms of age-related neuroanatomical changes and neuronal protection.
14
Dumesnil, Dennis. "Neurological Responses to a Glucose Diet in Caenorhabditis elegans." Thesis, University of North Texas, 2017. https://digital.library.unt.edu/ark:/67531/metadc1011786/.
Full textAbstract:
TRPV channels play a role in both mammalian insulin signaling, with TRPV1 expression in pancreatic beta-cells, and in C. elegans insulin-like signaling through expression of OSM-9, OCR-1, and OCR-2 in stress response pathways. In response to a glucose-supplemented diet, C. elegans are know to have sensitivity to anoxic stress, exhibit chemotaxis attraction, and display reduced egg-laying rate. Transcriptome analysis reveals that glucose stimulates nervous system activity with increased transcript levels of genes regulating neurotransmitters. Ciliated sensory neurons are needed for a reduced egg-laying phenotype on a glucose-supplemented diet. Egg-laying rate is not affected when worms graze on glucose-supplemented Delta-PTS OP50 E. coli, which is defective in glucose uptake. This suggests a possible sensory neuron obstruction by exopolysaccharides produced by standard OP50 E. coli on glucose, eliciting a starvation response from the worm and causing reduced egg-laying rate. Glucose chemotaxis is affected in specific TRPV subunit allele mutants: ocr-2(vs29) and osm-9(yz6), serotonin receptor mutants: ser-1(ok345) and mod-1(ok103), and G-alpha protein mutant: gpa-10(pk362). TRPV deletion mutants had no effect on glucose chemotaxis, alluding to the modality role pf TRPV alleles in specific sensory neurons. The role of serotonin in a reduced egg-laying rate with glucose remains unclear.
15
Millet, Jonathan. "Stratégies d'analyse spatio-temporelle de l‟épissage alternatif chez Caenorhabditis elegans." Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0437/document.
Full textAbstract:
L‟épissage alternatif est un mécanisme de régulation de l‟expression des gènes ayant pris une importance croissante dans l‟étude du vivant. Si des méthodes existent pour déterminer les gènes qui y sont soumis, peu d‟outils sont disponibles pour suivre ces événements d‟épissage in vivo au cours du développement. Pourtant, la caractérisation des régulations sous-jacentes à ces évènements et la détermination des facteurs impliqués sont dépendantes de stratégies fiables pour les visualiser dans des conditions physiologiques.Nous avons développé un système adapté à l‟étude d‟événements d‟épissage basé sur un rapporteur fluorescent bicolore. Nous l‟avons appliqué à cinq gènes de l‟organisme modèle Caenorhabditis elegans et avons suivi leur épissage in vivo.Parmi les différents gènes suivis, deux d‟entre eux suivaient un modèle d‟épissage potentiellement stochastique, un autre une absence d‟épissage alternatif détectable. Les deux derniers gènes présentent un profil d‟épissage spécifique à certain types cellulaires mais ont un effet toxique sur l‟organisme lorsque nous les avons exprimés à partir de concatémères extrachromosomiques. Pour remédier à cela, nous avons choisi de mettre en place une méthode simplifiée d‟insertion en simple copie des rapporteurs utilisant le CRISPR-Cas.Nos résultats indiquent que le système rapporteur fonctionne avec succès. Cependant, il peut encore être amélioré pour se rapprocher des taux physiologiques de transcription grâce à une insertion en simple copie dans le génome de l‟organisme. Nous avons également révélé un événement sous le contrôle de régulations spatiales, temporelles et conditionnelles. De plus, nous avons créé une série de constructions capables de déterminer les éléments en cis impliqués dans la régulation du gène top-1<br>Alternative splicing is a regulatory mechanism of gene expression which is increasingly studied in Life Science. Methods exist to study this mechanism but specific tools to follow each alternative splicing event in a spatio-temporal manner are lacking. Yet, the characterization of the regulation and the elements that determines them depends on valide strategies for visualising them in physiological conditions.We have developped a dual-fluorescent reporter-based system in order to follow alternative splicing event regulation in vivo. It has been applied to five different genes in the model organism Caenorhabditis elegans. Among the genes followed, two follow a potentially stochastic scheme, one show no visible sign of alternative splicing. The last display tissue specific splicing patterns but developed a toxic effect in the animal when expressed from a multicopy extrachromosomal array. To remediate this problem, we decided to develop a method that allows for simpler single copy insertion of fluorescent reporter using CRISPR-Cas.Our results indicates that the dual-fluorescent reporter works well. However, this system can be upgraded by getting close to physiological rates of transcription allowed by single-copy insertion in the genome of C.elegans. We also discovered an alternatiove splicing event which follows a spatial, temporal and conditionnal regulation. Moreover, we constructed a set of different reporter to unravel the regulation observed in the gene top-1
16
Soltesz, Zoltan. "Optogenetic investigation of the neural network underlying the oxygen modulation of C. elegans locomotion." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708419.
Full text
17
Clark, Christopher M. "Neural Orchestration of the C. elegans Escape Response: A Dissertation." eScholarship@UMMS, 2014. https://escholarship.umassmed.edu/gsbs_diss/750.
Full textAbstract:
How does a nervous system orchestrate compound behaviors? Finding the neural basis of behavior requires knowing which neurons control the behavior and how they are connected. To accomplish this we measured and manipulated neural activity in a live, behaving animal with a completely defined connectome. The C. elegans escape response is a compound behavior consisting of a sequence of behavioral motifs. Gentle touch induces a reversal and suppression of head movements, followed by a deep turn allowing the animal to navigate away from the stimulus. The connectome provides a framework for the neural circuit that controls this behavior. We used optical physiology to determine the activity patterns of individual neurons during the behavior. Calcium imaging of locomotion interneurons and motor neurons reveal unique activity profiles during different motifs of the escape response. Furthermore, we used optogenetics and laser ablations to determine the contribution of individual neurons to each motif. We show these that the suppression of head movements and turning motifs are distinct motor programs and can be uncoupled from the reversal. The molecular mechanisms that regulate these motifs involve from signaling with the neurotransmitter tyramine. Tyramine signaling and gap junctions between locomotion interneurons and motor neurons regulate the temporal orchestration of the turning motif with the reversal. Additionally, tyramine signaling through a GPCR in GABAergic neurons facilitates the asymmetric turning during forward viii locomotion. The combination of optical tools and genetics allows us to dissect a how a neural circuit converts sensory information into a compound behavior.
18
Clark, Christopher M. "Neural Orchestration of the C. elegans Escape Response: A Dissertation." eScholarship@UMMS, 2010. http://escholarship.umassmed.edu/gsbs_diss/750.
Full textAbstract:
How does a nervous system orchestrate compound behaviors? Finding the neural basis of behavior requires knowing which neurons control the behavior and how they are connected. To accomplish this we measured and manipulated neural activity in a live, behaving animal with a completely defined connectome. The C. elegans escape response is a compound behavior consisting of a sequence of behavioral motifs. Gentle touch induces a reversal and suppression of head movements, followed by a deep turn allowing the animal to navigate away from the stimulus. The connectome provides a framework for the neural circuit that controls this behavior. We used optical physiology to determine the activity patterns of individual neurons during the behavior. Calcium imaging of locomotion interneurons and motor neurons reveal unique activity profiles during different motifs of the escape response. Furthermore, we used optogenetics and laser ablations to determine the contribution of individual neurons to each motif. We show these that the suppression of head movements and turning motifs are distinct motor programs and can be uncoupled from the reversal. The molecular mechanisms that regulate these motifs involve from signaling with the neurotransmitter tyramine. Tyramine signaling and gap junctions between locomotion interneurons and motor neurons regulate the temporal orchestration of the turning motif with the reversal. Additionally, tyramine signaling through a GPCR in GABAergic neurons facilitates the asymmetric turning during forward viii locomotion. The combination of optical tools and genetics allows us to dissect a how a neural circuit converts sensory information into a compound behavior.
19
Ameen, Muhammad T., and Patrick C. Bradshaw. "VITAMIN B2 REDUCES AMYLOID-BETA PROTEOTOXICITY AND IMPROVES HEALTH IN A CAENORHABDITIS ELEGANS ALZHEIMER’S DISEASE MODEL." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/24.
Full textAbstract:
Alzheimer’s disease (AD) is a neurodegenerative disease and the most common form of dementia associated with amyloid-beta peptide deposition and loss of mitochondrial function and regulation. Currently, there is no cure for AD, thus, there is a need to continuously develop therapeutic strategies that could address the complex multifactorial causes of AD development. Due to this necessity, this study has investigated the role of vitamin B2 as a disease modifying drug for AD by employingamyloid-beta and mitochondrial based AD therapeutic strategies. Using a transgenic C. elegans AD worm model expressing amyloid-beta (Aβ1-42) in muscle cells at temperature upshift to 25°C, we screened for protective effect of dose-dependent concentrations of active forms of vitamin B2, FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide), against amyloid-beta mediated paralysis. Protective concentrations were then assayed for improvement of mitochondrial metabolic functions by performing ATP, oxygen consumption and reactive oxygen species (ROS) production assays. Consequently, we investigated for drug protective mechanisms of FMN and FAD using RNAi genetic screening technique. FMN and FAD significantly delayed amyloid-beta mediated paralysis and improved mitochondrial metabolic functions at final concentrations of 0.74mM and 0.74µM respectively. More so, both compounds induced activation of stress response FOXO transcription factor, daf-16. Specifically, FMN treatment induced mitochondrial unfolded protein response (UPRmt) pathway through ubiquitin-like protein (ubl-5) activation as well as other stress response pathway signature such as Activating Transcription Factor Associated with Stress (atfs-1). This study will be useful in understanding the importance of micronutrients such as vitamin B2 in normal cellular function as related to neurodegenerativediseases and aging. Therefore, vitamin B2 supplementation could be an important source of Alzheimer’s disease therapeutic strategy.
20
Ameen, Muhammad Tukur. "A Role of Vitamin B2 in Reducing Amyloid-beta Toxicity in a Caenorhabditis elegans Alzheimer’s Disease Model." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/etd/3398.
Full textAbstract:
Alzheimer’s disease (AD) is associated with amyloid-beta peptide deposition and loss of mitochondrial function. Using a transgenic C. elegans AD worm model expressing amyloid-beta in body wall muscle, we determined that supplementation with either of the forms of vitamin B2, flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) protected against amyloid-beta mediated paralysis. FMN and FAD were then assayed to determine effects on ATP, oxygen consumption, and reactive oxygen species (ROS) with these compounds not significantly improving any of these mitochondrial bioenergetic functions. Knockdown of the daf-16/FOXO transcriptional regulator or the FAD synthase enzyme completely abrogated the protective effects of FMN and FAD, while knockdown of the mitochondrial unfolded protein response factors ubl-5 or atfs-1 also blocked the protective effects. Therefore, vitamin B2 supplementation could lead to the activation of conserved signaling pathways in humans to delay the onset and progression of neurodegenerative diseases such as AD.
21
Ficociello, Laura Faraco. "Neuronal Migration: Investigating Interactions of the Cytoplasmic Adaptor Protein MIG-10 in C. elegans." Digital WPI, 2008. https://digitalcommons.wpi.edu/etd-theses/41.
Full textAbstract:
Neuronal migration is an essential aspect of nervous system development; improper or incomplete neuronal migration can lead to debilitating disorders. The model organism Caenorhabditis elegans has 302 neurons and is ideal for studying nervous system development. The cytoplasmic adaptor protein, MIG-10, is necessary for the long range anteroposterior migration during embryogenesis of the neurons CAN, ALM, and HSN. Mutations in the mig-10 gene result in incomplete migrations of all three neurons. MIG-10 is a homologue of the vertebrate proteins lamellipodin and RIAM-1, which are involved in directing actin polymerization during axon outgrowth and guidance. RIAM-1 is known to interact with proteins from the Ras GTPase family. The MIG-10 protein has a pleckstrin homology (PH) domain, a Ras-associating (RA) domain, and a proline-rich region. We used a yeast two-hybrid system to investigate which Ras family proteins MIG-10 interacts with. Three isoforms of MIG-10, MIG-10A, MIG-10B, and MIG-10C, as well as the RAPH domain alone, were used as baits. No evidence of interaction was observed for any of the baits used. These results do not reject our hypothesis as the constitutively active Ras clones may need to be used or there may not be a direct interaction between MIG-10 and the Ras family members. We are currently screening a C. elegans cDNA library for interactions with all three isoforms of MIG-10. In the future we plan to investigate how MIG-10 may be involved in the WAVE/SCAR actin nucleation pathway.
22
Showemimo, Opeyemi F. "Vitamin B12 Deficiency Does Not Stimulate Amyloid-beta Toxicity in a Ceanorhabditis elegans Model of Alzheimer’s Disease." Digital Commons @ East Tennessee State University, 2021. https://dc.etsu.edu/etd/3869.
Full textAbstract:
Alzheimer’s disease (AD) is symptomized by amyloid-beta plaques in the brain and accounts for more than 65 percent of dementia cases. Vitamin B12 (cobalamin) deficiency can result in similar cognitive impairment and roughly 15% of the elderly are vitamin B12 deficient. Vitamin B12 deficiency results in the accumulation of toxic methylmalonic acid and homocysteine. Hyperhomocysteinemia is a strong risk factor for AD. To test if vitamin B12 deficiency stimulates amyloid-beta toxicity, Caenorhabditis elegans expressing amyloid-beta in muscle were fed either vitamin B12-deficient OP50-1 or vitamin B12-rich HT115(DE3) E. coli bacteria. Increased amyloid-beta toxicity was found in worms fed the 0P50-1 diet. Supplementation of the OP50-1 diet with vitamin B12 did not rescue the increased C. elegans toxicity. Knockdown of either of the only two C. elegans vitamin B12-dependent enzymes metr-1 or mmmc-1 protected against toxicity. Therefore, vitamin B12 deficiency does not stimulate Alzheimer’s amyloid-beta-mediated toxicity in C. elegans.
23
Petrash, Hilary A. "Maintaining the Balance: Coordinating Excitation and Inhibition in a Simple Motor Circuit: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/633.
Full textAbstract:
The generation of complex behaviors often requires the coordinated activity of diverse sets of neural circuits in the brain. Activation of neuronal circuits drives behavior. Inappropriate signaling can contribute to cognitive disorders such as epilepsy, Parkinson’s, and addiction (Nordberg et al., 1992; Quik and McIntosh, 2006; Steinlein et al., 2012). The molecular mechanisms by which the activity of neural circuits is coordinated remain unclear. What are the molecules that regulate the timing of neural circuit activation and how is signaling between various neural circuits achieved? While much work has attempted to address these points, answers to these questions have been difficult to ascertain, in part owing to the diversity of molecules involved and the complex connectivity patterns of neural circuits in the mammalian brain.
My thesis work addresses these questions in the context of the nervous system of an invertebrate model organism, the nematode Caenorhabditis elegans. The locomotory circuit contains two subsets of motor neurons, excitatory and inhibitory, and the body wall muscle. Dyadic synapses from excitatory neurons coordinate the simultaneous activation of inhibitory neurons and body wall muscle. Here I identify a distinct class of ionotropic acetylcholine receptors (ACR-12R) that are expressed in GABA neurons and contain the subunit ACR-12. ACR-12R localize to synapses of GABA neurons and facilitate consistent body bend amplitude across consecutive body bends. ACR-12Rs regulate GABA neuron activity under conditions of elevated ACh release. This is in contrast to the diffuse and modulatory role of ACR-12 containing receptors expressed in cholinergic motor neurons (ACR-2R) (Barbagallo et al., 2010; Jospin et al., 2009). Additionally, I show transgenic animals expressing ACR-12 with a mutation in the second transmembrane domain [ACR-12(V/S)] results in spontaneous contractions. Unexpectedly, I found expression of ACR-12 (V/S) results in the preferential toxicity of GABA neurons. Interestingly loss of presynaptic GABA neurons did not have any obvious effects on inhibitory NMJ receptor localization. Together, my thesis work demonstrates the diverse roles of nicotinic acetylcholine receptors (nAChRs) in the regulation of neuronal activity that underlies nematode movement. The findings presented here are broadly applicable to the mechanisms of cholinergic signaling in vertebrate models.
24
Anvari, Sara. "Evaluation of virulence in wild type and pyrimidine auxotrophs of Pseudomonas aeruginosa using the eukaryotic model system Caenorhabditis elegans." Thesis, University of North Texas, 2004. https://digital.library.unt.edu/ark:/67531/metadc5561/.
Full textAbstract:
The human opportunistic pathogen, Pseudomonas aeruginosa PAO1, has been shown to kill the nematode Caenorhabditis elegans. C. elegans has been a valuable model for the study of bacterial pathogenesis, and has reinforced the notion that common virulence and host defense mechanisms exist. Recently, the pyrimidine pathway was shown to regulate virulence levels. Therefore, mutations in the pyrimidine pathway of PAO1 showed decrease virulence in the nematode. When starving the nematode, bacterial resistance was also shown to increase. It was hypothesized that starvation induced the DAF pathway, which regulates the transcription of genes involved with the antibacterial defense mechanism. Further research will be conducted to test this theory by performing RNAi experiments for the genes functioning in the antibacterial defense mechanism.
25
Holmgren, Benjamin T. "Connecting Systemic RNAi to the Endomembrane System in Caenorhabditis elegans." Doctoral thesis, Uppsala universitet, Mikrobiologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-320897.
Full textAbstract:
RNA interference (RNAi) is a gene regulation mechanism conserved among eukaryotes. To silence gene expression, RNAi relies on a short single-stranded guide RNA to steer the RNA-induced Silencing Complex (RISC) to mRNAs with guide strand-complementary sequences. RNAi is a highly membrane-associated process. The RISC complex is likely loaded at the rough Endoplasmic Reticulum, where it can bind to and degrade mRNAs. Components of the RISC complex also colocalize to late endosomes, and the efficiency of RNAi-mediated silencing is affected by changes in late endosome to lysosome fusion. RNAi can be systemic and inherited, effecting gene silencing in distal tissues and in the offspring. In this thesis, the model organism Caenorhabditis elegans was used to identify and characterize factors connecting systemic and inherited RNAi to the endomembrane system. We identify two SNARE proteins, SEC-22 and SYX-6, that both act as negative regulators of RNAi. SNAREs are necessary for vesicle fusion. Both SEC-22 and SYX-6 localize to late endosomes, and both interact with systemic RNAi protein SID-5 in a yeast two-hybrid (Y2H) screen. We find that in addition to its function in systemic RNAi, SID-5 is required for proper maturation of late endosomes. Furthermore, we identify the putative RNA-binding protein C12D8.1 as a novel regulator of RNAi inheritance. Mutant C12D8.1 animals will have enhanced inheritance of RNAi silencing, which negatively affects the ability of the progeny to silence new targets using RNAi. Finally, we describe a novel, object-based method for estimating significance in colocalization studies. This method helped us describe and quantify spatial relations between fluorophore-labeled proteins in situations where such analyses would otherwise be impossible. In conclusion, the work presented here further elucidates the connection between cellular RNAi, the endomembrane system, and the outside world.
26
Zhao, Yani. "Systemic RNAi Relies on the Endomembrane System in Caenorhabditis elegans." Doctoral thesis, Uppsala universitet, Mikrobiologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-330894.
Full textAbstract:
The membrane system of a eukaryotic cell is a large and complex system handling the transport, exchange and degradation of many kinds of material. Recent research shows that double-stranded RNA (dsRNA) mediated gene silencing (RNA interference) is a membrane related process. After long dsRNA is processed to small interfering RNA (siRNA) by Dicer, the guide strand and passenger strand are separated in the RNA induced silencing complex (RISC) by Argonaute. The process of loading siRNA into RISC has been suggested to occur at the rough Endoplasmic Reticulum (rER).The components of RISC also associate with late endosomes/multivesicular bodies (MVBs). Furthermore, disturbing the balance between late endosomes/MVBs and lysosomes has been shown to affect the efficiency of silencing. We use the nematode Caenorhabditis elegans as our model organism to study two questions: how does membrane transport affect RNAi and spreading of RNAi from the recipient cells to other tissues (systemic RNAi); and how does RNA transport contribute to the multigenerational silencing induced by dsRNA (RNAi inheritance)? Using SID-5, a protein required for efficient systemic RNAi, as bait in a yeast two-hybrid (Y2H) screen, we got 32 SID-5 interacting candidate proteins. Two of these are the SNARE protein SEC-22 and the putative RNA binding protein C12D8.1. In two additional Y2H screens, we found that SID-5 interacts with multiple syntaxin SNAREs, including SYX-6, whereas SEC-22 only interacts with SYX-6. SNAREs usually function in vesicle fusion processes. We found the two SNARE proteins SEC-22 and SYX-6 to be negative regulators of RNAi and to localize to late endosomes/MVBs. In addition, loss of sid-5 leads to an endosome maturation defect. Finally, we found that the putative RNA binding protein C12D8.1 negatively regulates RNAi inheritance and that C12D8.1 mutant animals show impaired RNAi upon targeting a new gene. Taken together, the results presented in this thesis provide us with more evidence for the connection of the membrane transport system and RNAi. The identification of a putative negative regulator of RNAi inheritance further enriches this research field.
27
Bender, Aaron. "Involvement of lin-35/Rb in C. elegans reproductive system development." Laramie, Wyo. : University of Wyoming, 2006. http://proquest.umi.com/pqdweb?did=1188872161&sid=2&Fmt=2&clientId=18949&RQT=309&VName=PQD.
Full text
28
Kindt, Katherine. "Monoamines, mechanosensation and memory in the C. elegans nervous system." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3232323.
Full textAbstract:
Thesis (Ph. D.)--University of California, San Diego, 2006.<br>Title from first page of PDF file (viewed December 4, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
29
Aida, Adlimoghaddam. "Molecular and physiological characterization of the nitrogen transport system in Caenorhabditis elegans." Journal of experimental biology (JEB), 2014. http://hdl.handle.net/1993/30721.
Full textAbstract:
In this study, we investigated the mechanism of nitrogen excretion in the soil nematode Caenorhabditis elegans. Utilizing the scanning ion electrode technique (SIET), it was shown for the first time in nematodes that the excretory cell promotes a secretion of ions, including Na+, K+, H+ and Ca2+. In addition, observations from experiments exposing the animal to various environmental pH regimes suggested that the mode of ammonia excretion is dependent on acidification of the unstirred boundary layer, supported also by a detected H+-net-excretion over the hypodermis employing SIET. Pharmacological experiments, SIET and enzyme activity measurements implicated the participation of a functional microtubule network, V-type H+-ATPase, carbonic anhydrase, Na+/K+-ATPase, and apical Na+-channels in the ammonia excretion mechanism of this roundworm. Most importantly, employing ammonia transporter deficient Saccharomyces cerevisiae we were able to show for the first time that an invertebrate Rh-like protein (Rhr-1) does indeed function as an ammonia transporter. Further, a second Rh-protein, Rhr-2, was found to be predominantly expressed in the hypodermis. Knock-out experiments on this transporter further suggested participation of Rhr-2 in the apical ammonia trapping mechanism. Overall, the results of this study provided evidence for a novel ammonia excretion mechanism over the hypodermis, which exhibits features commonly seen in both freshwater (ammonia trapping) and seawater inhabiting species (vesicular transport and exocytosis).<br>October 2015
30
Chow, Yit Lai. "Caenorhabditis elegans as a whole organism screening system for isoquinoline alkaloid bioactivities." 京都大学 (Kyoto University), 2014. http://hdl.handle.net/2433/188834.
Full text
31
Worrall, Liam. "Structural and biochemical studies of the Caenorhabditis elegans Hsp70/Hsp90 chaperone system." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/14705.
Full textAbstract:
This work presents the crystal structure of the C-terminal 10 kDa- sub-domain from <i>C. elegans</i> Hsp70. Despite a high degree of sequence identity, the <i>C. elegans</i> domain is shown to adopt a conformation distinct from the rat crystal structure, consistent with the more distantly related bacterial homologous. Comparison with the rat structure reveals an intriguing putative domain-swap dimerisation mechanism though the isolated <i>C. elegans</i> domain was found to exist exclusively as a monomer in solution. A previous study identified two TPR domain containing <i>C. elegans</i> putative proteins predicted to interact with Hsp90. These proteins were identified as the <i>C. elegans</i> homologues for small glutamine-rich TPR containing protein (SGT) and Hsp70/Hsp90 organising protein (HOP). These proteins have been successfully cloned, expressed and purified. SGT forms homo-dimers in solution. Its hydrodynamic dimensions in relation to its molecular weight suggest a protein with a low level of compactness and an extended conformation. SGT interacts with the C-terminal peptides from both Hsp70 and Hsp90 with equal affinities. Studies on <i>C. elegans</i> HOP suggested it might exist as a dimer in solution. In addition, a tight binding interaction was demonstrated with human and <i>C. elegans</i> Hsp90 homologues. A thorough search of the complete <i>C. elegans</i> proteome and genome was performed to identify the complete repertoire of TPR domain containing proteins likely to interact with Hsp70 or Hsp90. A profile HMM based search of the published <i>C. elegans</i> protein and DNA databases identified 12 proteins; nine of which are homologues of proteins known to interact with Hsp70 or Hsp90. The remaining three are uncharacterised putative proteins and represent targets for further study.
32
Gill, Stephen George. "Characterisation of the COP9 signalosome (CSN) using Caenorhabditis elegans as an experimental system." Thesis, University of Sussex, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418716.
Full text
33
James, Claerwen Laura. "Analysis of components of the Caenorhabditis elegans cell death apparatus in a heterologous system." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300783.
Full text
34
Jedrusik-Bode, Monika. "Molekulare Analyse der differentiellen Funktionen von Linkerhiston-Isoformen bei Caenorhabditis elegans." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=964334933.
Full text
35
Longhi-Browne, Cassandra W. "Using Caenorhabditis elegans as a novel expression system for the generation of recombinant Teladorsagia circumcincta vaccine candidates." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5547/.
Full textAbstract:
Teladorsagia circumcincta is a common abomasal parasite of sheep in temperate regions and is one of the major causes of parasitic gastroenteritis (PGE) in growing lambs. Control of infection is achieved using anthelmintic drugs; however, this practice is rapidly becoming unsustainable due to widespread anthelmintic resistance within the T. circumcincta population. Sheep can acquire protective immunity against this parasite; immunity involves local and systemic antibodies and immune cells which can impair worm growth and fecundity and lead to expulsion of the parasites from the abomasum. Vaccination against this parasite is therefore a feasible option of control. A recent study showed that a recombinant vaccine cocktail containing 8 T. circumcincta antigens significantly reduced the faecal egg count and worm burdens of immunised sheep, compared to an adjuvant-only control group. However, the recombinant antigens induced a suboptimal antibody response to the recombinant antigens. This suggests that differencies between the native antigens and their recombinant versions may exist, possibly due to variations in structure and/or post-translational modifications (PTMs). The main aim of this work was to use a novel expression system, the free living nematode Caenorhabditis elegans, to generate alternative recombinant versions of two of the T. circumcincta antigens used in the 8-antigen vaccine, cathepsin F (Tci-CF-1) and monocyte Migration Inhibitory Factor (Tci-MIF-1). This was achieved by micro-injection of C. elegans worms with plasmids containing the cDNA sequences of Tci-cf-1 and Tci-mif-1 followed by purification of recombinant Tci-CF-1 and Tci-MIF-1 from the transformed worms. Immune recognition, enzyme activity and biological effects on sheep cells of the recombinant antigens were characterised. The results show that immunisation-induced antibodies bind to native Tci-CF-1 purified from T. circumcincta L4 ES, whereas infection-induced antibodies were unable to bind the recombinant Tci-CF-1 versions. Further characterisation of recombinant Tci-CF-1 versions expressed in C. elegans or Pichia pastoris showed that in order to be enzymically active, these proteins require cleavage of the pro-peptide by an exogenous enzyme and that some differences were present in the glycosylation of the recombinant versions and native Tci-CF-1. Characterisation of both recombinant Tci-MIF-1 versions showed that although both are enzymically active, neither showed a significant inhibitory effect on the migration of sheep monocytes or on the activation of sheep macrophages in vitro compared to unstimulated controls. It is speculated that Tci-MIF-1 may be involved in T. circumcincta larval development rather than host immunosuppression.
36
Lanthrop, Jeremy R. "Identification of proteins that interact with CeABF-1 using A yeast two-hybrid system." Scholarly Commons, 2004. https://scholarlycommons.pacific.edu/uop_etds/3101.
Full textAbstract:
The helix-loop-helix (HLH) family of transcription regulatory proteins are fundamental regulators in the processes of cell proliferation and differentiation, cell lineage determination, myogenesis, neurogenesis, and sex determination in a wide range of multicellular organisms. A gene encoding a novel class II HLH protein has recently been identified from a human B-cell eDNA library using a yeast two-hybrid screen. The predicted human ABF -1 polypeptide sequence was used to search the Caenorhabditis elegans genome database for a C. elegans ABF-1 homolog. This bHLH protein, called C. elegans ABF -1 (CeABF -1 ), has a bHLH domain that shares 72% amino acid similarity with its human ABF-1 relative. The expression of the CeABF-1 mRNA has been detected in larval stages L2, L3, L4, and adult, however the mRNA is most highly expressed at the L3 and L4 stages. CeABF -1 protein is capable of heterodimerizing with the human E2A gene product, E4 7. Like human ABF -1, CeABF -1 expression in the presence of the E4 7 protein results in a reduction in E2A mediated gene activation. It has therefore been concluded that CeABF -1 , like human ABF -1 , also acts as a transcriptional
repressor. Because C. elegans shares many conserved genes with higher eukaryotic organisms it has become a model organism for in depth genetic studies. It has therefore become increasingly desirable to investigate the possibility of alternative protein-protein interactions that can potentially occur within C. elegans, so it was necessary to construct a C. elegans eDNA library along with the appropriate bait vector expressing the CeABF- 1 protein. The titer ofthe primary library was calculated to be 9.7 x I06 clones, 10-fold greater than minimum titer requirement of I x I 06 clones for a good representational library. Sequencing of the CeABF -I insert confirmed successful construction of a mutation-free bait construct suitable for use in yeast two-hybrid screening. Yeast-two hybrid analysis revealed two new interactors, one of which was identified as an aldose reductase homolog, while the other remains uncharacterized.
37
Eckl, Julia Martina [Verfasser], Klaus [Akademischer Betreuer] Richter, and Michael [Akademischer Betreuer] Sattler. "Analysis of the Hsp90 client system in Caenorhabditis elegans / Julia Martina Eckl. Gutachter: Michael Sattler ; Klaus Richter. Betreuer: Klaus Richter." München : Universitätsbibliothek der TU München, 2014. http://d-nb.info/1076124860/34.
Full text
38
Guha, Sanjib Kumar 1984. "A. C. elegans model for X-linked adrenoleukodystrophy : roles of pmp-4 fatty acid transporter in the nervous system." Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/328717.
Full textAbstract:
X-linked adrenoleukodystrophy (X-ALD) is an inherited neurodegenerative disorder. The genetic bases for all its different phenotypic variants are mutation in the gene encoding the peroxisomal ATP-binding cassette (ABC) transporter ABCD1, which transports very long chain fatty acids from the cytosol into the peroxisome for its degradation. The default manifestation of mutation in ABCD1 is adreno myeloneuropathy (AMN), a slow, progressive dying-back axonopathy affecting both ascending and descending spinal cord tracts as well as in some cases, peripheral neuropathy. In the present study, we use the invertebrate model organism Caenorhabditis elegans to generate a new nematode model of X-ALD. We reveal that the pmp-4(ok396) deletion mutant reproduces the main features of X-ALD such as lipid accumulation, increased mitochondrial oxidative stress, axonopathy and altered locomotion. Given the evidence that oxidative stress plays an important role in VLCFA-induced pathogenesis of ALD, therapeutic efforts aimed at the removal of free-radicals, prevention of their formation, or restoration of ETC function seem promising. Indeed, here we describe the mitochondria-specific pharmacological effects of MitoQ in protecting against VLCFA-induced toxicity and oxidative stress and its ability to rescue the observed X-ALD phenotypes on pmp-4(ok396) mutant worms.<br>La adrenoleucodistrofia ligada al cromosoma X (ALD-X) es un trastorno neurodegenerativo hereditario, causado por mutaciones en ABCD1. Este gen codifica para un transportador peroxisomal que importa ácidos grasos de cadena muy larga (AGCML) del citosol hacia el peroxisoma para su posterior degradación. La adrenomieloneuropatía (AMN) es la variante fenotípica en adultos y se manifiesta como un axonopatia de progresión lenta en la médula espinal. En este estudio utilizamos el gusano Caenorhabditis elegans para generar un nuevo modelo de ALD-X. Observamos que el mutante pmp-4(ok396) reproduce las principales características de la ALD-X (acumulación de lípidos, incremento del estrés oxidativo mitocondrial, axonopatía y locomoción alterada). Basándonos en evidencias que el estrés oxidativo inducido por acumulación de AGCML juega un papel importante en la patogénesis, estrategias enfocadas en la eliminación de radicales libres, prevención de su formación o normalización de la función de la cadena de transporte de electrones mitocondrial, poseen un prometedor potencial terapéutico. Aquí demostramos que el compuesto MitoQ actua a nivel mitocondrial protegiendo en contra del estrés oxidativo y rescata los fenotipos ALD-X en los gusanos pmp-4(ok396).<br>La adrenoleucodistròfia lligada al cromosoma X (ALD-X) és un trastorn neurodegeneratiu hereditari, causat per mutacions en ABCD1. Aquest gen codifica per un transportador peroxisomal que importa àcids grassos de cadena molt llarga (AGCML) del citosol cap al peroxisoma per a la seva posterior degradació. La adrenomieloneuropatía (AMN) és la variant fenotípica en adults i es manifesta com una axonopatia de progressió lenta en la medul•la espinal. En aquest estudi utilitzem el cuc Caenorhabditis elegans per generar un nou model d'ALD-X. Observem que el mutant pmp-4 (ok396) reprodueix les principals característiques de l'ALD-X (acumulació de lípids, increment d'estrès oxidatiu mitocondrial, axonopatia i locomoció alterada). Basant-nos en les evidències que l'estrès oxidatiu induït per acumulació d’AGCML juga un paper important en la patogènesi, estratègies enfocades en eliminar radicals lliures, prevenirla seva formació o normalitzar la funció de la cadena de transport d'electrons mitocondrial, posseeixen un prometedor potencial terapèutic. Aquí, demostrem que el compost MitoQ actua a nivell mitocondrial protegint en contra de l'estrès oxidatiu i rescatant els fenotips ALD-X en els cucs pmp-4 (ok396).
39
Nakano, Shunji Ph D. Massachusetts Institute of Technology. "Chromatin and transcriptional regulators act in a cascade to establish a bilateral asymmetry of the C. elegans nervous system." Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/62621.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, February 2011.<br>This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.<br>"October 2010." Student received a Ph. D. per February 2011 MIT Degree List, Office of the Registrar. Cataloged from student-submitted PDF version of thesis.<br>Includes bibliographical references.<br>Neuroanatomical bilateral asymmetry is a widespread feature in both vertebrates and invertebrates. Although mostly bilaterally symmetric, the nervous system of Caenorhabditis elegans displays bilateral asymmetry. Bilateral asymmetry in C. elegans arises in part from left-right asymmetric cell lineages. The single left-right unpaired MI neuron is normally generated from the right side of an otherwise left-right symmetric cell lineage that on the left gives rise to the e3D epithelial cell. We performed genetic screens and isolated mutants that displayed symmetry in this normally asymmetric cell lineage, with the MI neuron transformed into an e3D-like cell. We identified that a C. elegans Otx homeodomain protein CEH-36 and two basic helix-loop-helix proteins NGN-1 and HLH-2 promote the generation of the MI neuron and are required to establish the bilateral asymmetry in this cell lineage. We found that CEH-36 is asymmetrically expressed and is present in an MI precursor cell on the right but not in an e3D precursor cell on the left. This bilaterally asymmetric CEH-36 expression in turn promotes asymmetric NGN-1 and HLH-2 expression, leading to the generation of the MI neuron on the right side of the cell lineage. The Otx/bHLH transcriptional cascade is evolutionarily conserved, and our results suggest that this transcriptional cascade plays a role in establishing neuroanatomical bilateral asymmetry in other animals. We also discovered that a mutation in a replication-dependent histone H3 gene his-9 transforms the MI neuron into an e3D-like cell. This mutant allele of his-9 causes an altered-function activity that is predicted to impair the interaction of the mutant HIS-9 protein with another histone H3 molecule and inhibit the formation of a histone H3-H4 tetramer. Replication-dependent histones H3-H4 are deposited onto replicating DNA by the heterotrimeric protein complex CAF-1. We observed that loss of function of each of three genes encoding members of the C. elegans CAF-1 complex transformed MI into an e3D-like cell. We propose that CAF-1-mediated nucleosome formation is impaired by the presence of mutant HIS-9 proteins that are unable to form the histone H3-H4 heterotetramer. We also found that two histone-modifying enzymes SET-16 and UTX-1 are required to establish the bilateral asymmetry in this cell lineage. set-16 encodes a protein homologous to the human MLL protein, a histone methyltransferase specific for histone H3 lysine 4, and utx-1 encodes a protein homologous to human UTX protein, a histone demethylase specific for histone H3 lysine 27. Our results reveal a novel mechanism of establishing neuroanatomical bilateral asymmetry and suggest that nucleosome formation and histone H3 modification are required to establish this bilateral asymmetry.<br>by Shunji Nakano.<br>Ph.D.
40
Oliver, Devyn. "Constructing and Maintaining the Nervous System: Molecular Insights Underlying Neuronal Architecture, Synaptic Development, and Synaptic Maintenance Using C. elegans." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1123.
Full textAbstract:
In the nervous system, billions of neurons undergo a multistep process to establish functional circuits. This entails accurate extension of dendritic and axonal processes and coordinated efforts of pre- and postsynaptic neurons to form synaptic connections. Although many axon guidance molecules and synaptic organizers have been identified, the molecular redundancy and the vast number of synapses in the brain has complicated attempts to define their precise roles. In order to understand the molecular mechanisms that encompass these processes, my studies utilize the genetic strengths and cellular precision available in Caenorhabditis elegans for in vivo investigations of nervous system development. In this work, I unravel cell-specific requirements for the transmembrane receptor integrin in regulating developmental axon guidance of GABAergic motor neurons. Furthermore, I address important questions about mechanisms of synapse formation and maintenance using a novel dendritic spine model in C. elegans. Using high resolution microscopy, I find that the formation of immature presynaptic vesicles and postsynaptic receptors are established prior to the outgrowth of dendritic spines at nascent synapses. During this early period of synapse formation, the kinesin-3 family protein UNC-104/KIF1A transports a transsynaptic adhesion molecule neurexin/NRX-1 to developing active zones, in order to maintain postsynaptic receptors and dendritic spines in the mature circuit. In the absence of nrx-1, spines initially form normally but collapse following their extension. These findings demonstrate that presynaptic NRX-1 is required to maintain postsynaptic structures. Together my work provides new insights into molecular mechanisms that define spatiotemporal characteristics of nervous system development and the maintenance of connectivity.
41
Hoop, Alyssa N. "Rho-Family GTPase Signaling in the Nervous System: An Analysis of the C. elegans RhoGEF UNC-73." University of Toledo / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404733888.
Full text
42
Rajakumar, Vandana. "Study of the Role of EGL-38 PAX in the Developing Egg-Laying System and Germline Cell Survival in Caenorhabditis Elegans." The Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1166929817.
Full text
43
Tsushima, Hanako. "A study of the interactors of Eps15 homology domain and the role of the EH network in the model system of Caenorhabditis elegans." Thesis, Open University, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497396.
Full textAbstract:
Epsl5 homology (EH) domain-containing proteins have been implicated in diverse intracellular signalling pathways, such as endocytosis, actin cytoskeleton organization, nucleo-cytosolic shuttling and mitogenic signalling. However, the extent of the protein-protein interactions mediated by the EH domain at the level of a whole organism has not yet been addressed. This project aims to gain an overview of the EH network in a model system, C. elegans, by identifying interactors of all EH-domain containing proteins present in C. elegans. Five genes encode EH proteins in the C. elegans genome and the isolated EH domains were used to screen a C. elegans cDNA library using the Yeast Two Hybrid system. The validation of the putative interactions was carried out by in vitro pull-down assays. The biological relevance of the interactions was tested genetically using C elegans as a model system. The genetic interactions were monitored using available mutants for four of the five EH encoding genes, in which the genes of the putative interactors were knocked-down by RNA interference.
44
Towlson, Emma Katie. "Complex networks and connectomics : network analysis of organisation from the C. elegans nervous system to the functional connectivity of the human brain." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709453.
Full text
45
Armstrong, Kristin R. "Multiple Mechanisms Contribute to Regulation of Gene Expression in the C. elegans Excretory System." Columbus, Ohio : Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1214071705.
Full text
46
Kim, Soyoung. "A Study of Cell Polarity and Fate Specification in Early C. Elegans Embryos: A Dissertation." eScholarship@UMMS, 2008. https://escholarship.umassmed.edu/gsbs_diss/385.
Full textAbstract:
Asymmetric cell divisions constitute a basic foundation of animal development, providing a mechanism for placing specific cell types at defined positions in a developing organism. In a 4-cell stage embryo in Caenorhabditis elegansthe EMS cell divides asymmetrically to specify intestinal cells, which requires a polarizing signal from the neighboring P2 cell. Here we describe how the extracellular signal from P2 is transmitted from the membrane to the nucleus during asymmetric EMS cell division, and present the identification of additional components in the pathways that accomplish this signaling.
P2/EMS signaling involves multiple inputs, which impinge on the Wnt, MAPK-like, and Src pathways. Transcriptional outputs downstream of these pathways depend on a homolog of β-catenin, WRM-1. Here we analyze the regulation of WRM-1, and show that the MAPK-like pathway maintains WRM-1 at the membrane, while its release and nuclear translocation depend on Wnt/Src signaling and sequential phosphorylation events by the major cell-cycle regulator CDK-1 and by the membrane-bound GSK-3 during EMS cell division. Our results provide novel mechanistic insights into how the signaling events at the cortex are coupled to the asymmetric EMS cell division through WRM-1.
To identify additional regulators in the pathways governing gut specification, we performed suppressor genetic screens using temperature-sensitive alleles of the gutless mutant mom-2/Wnt, and extra-gut mutant cks-1. Five intragenic suppressors and three semi-dominant suppressors were isolated in mom-2 suppressor screens. One extragenic suppressor was mapped to the locus ifg-1, eukaryotic translation initiation factor eIF4G. From the suppressor screen using cks-1(ne549), an allele of the self-cleaving nucleopore protein npp-10 was identified as a suppressor of cks-1(ne549)and other extra-gut mutants.
Taken together, these results help us better understand how the fate of intestinal cells are specified and regulated in early C. elegans embryos and broaden our knowledge of cell polarity and fate specification.
47
Desbois, Muriel. "Dynamic synaptic changes revealed by a novel trans-synaptic method to visualize connections in vivo in C. elegans." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066157/document.
Full textAbstract:
Le système nerveux est un réseau complexe qui détecte et analyse les informations. Ces informations sont transmises entre cellules grâce à des connections synaptiques et des jonctions communicantes. Ce réseau n’est pas statique et évolue au cours du développement, de l’apprentissage mais aussi durant le processus de vieillissement – naturels ou pathologiques. Comprendre le système nerveux et son fonctionnement requiert une analyse des connections synaptiques in vivo chez un animal model tel que Caenorhabditis elegans. Cependant les techniques actuellement disponibles pour C. elegans sont laborieuses, ne dépendent pas forcément d’une interaction trans-synaptique ou fixent la synapse. Par conséquent, ces approches ne permettent pas de réaliser des études de populations et dynamiques des modifications synaptiques. Dans ce manuscrit, je décris tout d’abord une nouvelle technique pour visualiser les synapses in vivo chez le vers C. elegans. Cette technique appelé iBLINC (in vivo Biotin Labeling of INtercellular Contacts) qui consiste en la biotinylation d’un peptide par une ligase d’Escherichia coli, BirA. Ces deux molécules sont fusionnées à des protéines trans-membranaires qui forment un complexe à la synapse. La biotinylation est détectée grâce à une streptavidin monomérique taguée avec un fluorophore qui est secrétée dans l’espace extracellulaire. J’ai démontré que cette technique est directionnelle et dynamique. En utilisant iBLINC pour visualiser des synapses faisant partie du circuit sensoriel de C. elegans, une évolution du nombre et de la taille des synapses a pu être observée avec l’âge. Il semblerait que ce changement soit dépendant du segment de la zone synaptique observée. Ces résultats ont été corroborés par l’observation d’une diminution du nombre de vésicules pendant le vieillissement grâce à un marqueur pré-synaptique des synapses GABAergique de la jonction neuromusculaire. Pour conclure, ce manuscrit décrit une nouvelle technique permettant d’observer les synapses chez le vers vivant et démontre une évolution naturelle du nombre de synapses et du nombre de vésicules pré-synaptiques avec l’âge<br>The nervous system is a complex network that senses and processes information and is essential for the survival of both vertebrates and invertebrates as it is involved in behavior responses. Information within the network is transmitted through specialized cell-cell contacts, including synaptic connections. Importantly, the network is not static and is believed to change during development and learning, as well as during pathological or normal age-related decline. Studying the nervous system in vivo requires the use of animal models such as Caenorhabditis elegans. Understanding of behavior and development requires visualization and analysis of synaptic connectivity. However, existing methods are laborious and may not depend on trans-synaptic interactions, or otherwise ‘trap’ the synapses by fixing the connections, thus precluding dynamic studies. In order to study synaptic modifications, we developed a new transgenic approach for in vivo labeling of specific connections in C. elegans, called iBLINC (in vivo Biotin Labeling of INtercellular Contacts). iBLINC involves the biotinylation of an acceptor peptide (AP) by the Escherichia coli biotin ligase BirA. Both are fused to two interacting post- and pre-synaptic proteins, respectively. The biotinylated acceptor peptide fusion is detected by a monomer streptavidin fused to a fluorescent protein that is transgenically expressed and secreted into the extracellular space. The method is directional, bright and dynamic. Moreover it correlates well with electron micrograph reconstruction. Using this new technique to observe synapses, which are part of the thermosensory circuitry of C. elegans, during aging, we could conclude that the connection pattern varies with age and within a population. Changes of the number and size of the synapses were observed during aging. Some segments of the synaptic region seem to be more affected than others by the aging process. Those results were corroborated by using a GABAergic pre-synaptic marker which allowed us to visualize a decline of the vesicle number with aging. In summary, in this thesis I explained a new in vivo trans-synaptic method to visualize synapses in C. elegans. Then I demonstrated that a natural decline in the number of synapses as well as the number of vesicles occurs during aging
48
Bayer, Emily Ann. "Sexually Dimorphic Development of the Caenorhabditis elegans Nervous System." Thesis, 2020. https://doi.org/10.7916/d8-kcqy-1e23.
Full textAbstract:
Sexual reproduction is an evolutionary innovation that arose 1.2 billion years ago, and in that time, has allowed a rapid diversification of species outpacing that of asexually reproducing organisms. Successful sexual reproduction in animals requires the incredible coordination of complex genetic and behavioral factors; from the most fundamental levels of ensuring correct chromosome segregation and ploidy to the most complex of behavioral mating rituals, any failure can result in a complete loss of evolutionary fitness. In this thesis, I have explored the developmental programs that function to ensure somatic sex determination, sexual differentiation, and mating behaviors in C. elegans. C. elegans is an androdiecious nematode species that has been extensively characterized in regard to the sexual dimorphism of its development, nervous system, and behavioral outputs. Sex determination pathways are widely diverged across phyla, and C. elegans has coopted a Gli family transcription factor to serve as a cell autonomous global regulator of somatic sex determination. I investigated the expression of this transcription factor, tra-1, with cellular, subcellular, sex-specific, and temporal resolution in both sexes of C. elegans and found that it is dynamically regulated to control sex determination. In contrast to the upstream sex determination pathway, genes that control downstream sexual differentiation in animals display much higher functional conservation, and many of the regulators of sexual differentiation belong to a family of transcription factors known as the DMRT family. Downstream of the tra-1 global regulator, I found that the highly conserved DMRT family gene dmd-4 acts much more specifically in adult hermaphrodites to generate sexual dimorphism at the level of the phasmid sensory neurons PHA and PHB. Furthermore, the sexual dimorphism of DMD-4 is regulated post-translationally by a ubiquitin-binding domain that I also found to be functionally conserved in the human ortholog, Dmrt3. Although these transcription factors both demonstrate the high degree of genetic control that contributes to sex determination and sexual differentiation, I also described male-specific effects of early life stress on sexual dimorphic synaptic connectivity and behavior generated by the phasmid sensory neurons, indicating that sexual differentiation is also plastic to environmental cues encountered during the life of an organism. This thesis provides insight into how genetic pathways function at multiple levels to give rise to extensive sexual dimorphism in the soma of an animal, both globally and in regard to the development on individual cells, in addition to the ways in which these genetic pathways can be modified by environmental factors and organismal life history.
49
Berghoff, Emily Greta. "Circuit transcription factors in Caenorhabditis elegans." Thesis, 2020. https://doi.org/10.7916/d8-77a8-5z43.
Full textAbstract:
Many neuronal patterning genes are expressed in distinct populations of cells in the nervous system, leading researchers to analyze their function in specific isolated cellular contexts that often obscure broader, themes of gene function. In this thesis, I aim to make clearer those overlooked common functional themes. I show that the C. elegans homeobox gene unc-42 is expressed in 15 out of a total of 118 distinct sensory, inter, and motor neuron classes throughout the C. elegans nervous system. Of these 15 unc-42(+) synaptically interconnected neuron classes, I show the extent to which unc-42 controls their identities and assembly into functional circuitry. I find that unc-42 defines the routes of communication between these interconnected neurons by controlling the expression of neurotransmitter pathway genes, neurotransmitter receptors, neuropeptides and neuropeptide receptors. I also show that unc-42 controls the expression of molecules involved in axon pathfinding and cell-cell recognition. Consequently, I show how the loss of unc-42 has effects on axon pathfinding and chemical synaptic connectivity, as determined by electron microscopical reconstruction of serial sections of unc-42 mutants. I conclude that unc-42 plays a critical role in establishing functional circuitry by acting as a terminal selector of functionally connected neuron types. I speculate that in other parts of the nervous system “circuit transcription factors” may also control assembly of functional circuitry and propose that such organizational properties of transcription factors may be reflective of not only an ontogenetic, but perhaps also phylogenetic trajectory of neuronal circuit establishment.
50
Weinberg, Peter J. "Mechanisms of sexually dimorphic development in the nervous system of Caenorhabditis elegans." Thesis, 2017. https://doi.org/10.7916/D8N302MV.
Full textAbstract:
The advent of sexual reproduction in early evolutionary history had profound effects on the evolution of animals. In most sexually reproducing species, males and females have distinct morphological and behavioral differences that are shaped by the evolutionary imperatives of each sex. Underlying the behavioral differences between males and females are distinct and measurable dimorphisms in the nervous system. These dimorphisms can arise in the form of connectivity, neurotransmitter usage, gene expression or combinations of all three. The androdioecious nematode Caenorhabditis elegans, with its stereotyped development and simple nervous system, offers a remarkably powerful system for studying the conserved mechanisms of sex determination that shape neural development. In this thesis, I present my work on the characterization of several genes that regulate the development of sexual dimorphisms in the nervous system. The first part of the thesis concerns the characterization of the gene ham-3, which codes for a subunit of the C. elegans ortholog of the SWI/SNF chromatin remodeling complex. ham-3 is required for the proper terminal differentiation of the HSN, a serotonergic neuron of the sex-specific nervous system, which it manages by regulating the expression of transcription factors required for crucial steps
of migration, axon guidance and serotonergic fate adoption. The second part of the thesis concerns the investigation of sexually dimorphic pruning mechanisms. I show that unc-6/Netrin is subject to direct transcriptional repression in hermaphrodites by tra-1, the master transcriptional regulator of sexual fate determination in C. elegans. This regulation is required for the proper timing of the sexually dimorphic pruning of synapses in the tail region in hermaprhodites. In males, where unc-6 is not repressed by tra-1, unc-6 expression perdures into adulthood and the synapse is maintained. Together, these data provide insight into the ways in which conserved genetic and developmental mechanisms manage the generation differentiation, connectivity, and maintenance of sexually dimorphic nervous systems.