Littérature scientifique sur le sujet « Caenorhabditis elegans – Système nerveux »

Abstract Matrices are two-dimensional data structures allowing one to conceptually organize information [1]. For example, adjacency matrices are useful to store the links of a network; correlation matrices are simple ways to arrange gene co-expression data or correlations of neuronal activities [2, 3]. Clustering matrix values into geometric patterns that are easy to interpret [4] helps us to understand and explain the functional and structural organization of the system components described by matrix entries. Here we introduce a theoretical framework to cluster a matrix into a desired pattern by performing a similarity transformation obtained by solving a minimization problem named the optimal permutation problem. On the computational side, we present a fast clustering algorithm that can be applied to any type of matrix, including non-normal and singular matrices. We apply our algorithm to the neuronal correlation matrix and the synaptic adjacency matrix of the Caenorhabditis elegans nervous system by performing different types of clustering, including block-diagonal, nested, banded, and triangular patterns. Some of these clustering patterns show their biological significance in that they separate matrix entries into groups that match the experimentally known classification of C. elegans neurons into four broad categories, namely: interneurons, motor, sensory, and polymodal neurons.

Cette étude sur la locomotion de C. Elegans vise à mieux comprendre le fonctionnement de son système nerveux et à apporter des éléments nouveaux de réflexion pour la conception de modèles ou d'objet biomimétiques. Ce travail débute par une description du ver, de sa physiologie ainsi que des principaux modes de locomotion connus : la nage (en milieu liquide) et la reptation (sur gel aqueux). Puis dans le cas de la nage, nous mettons en évidence une dissymétrie du mouvement, nécessaire pour la progression en milieu visqueux. L'analyse des vitesses des déplacements locaux permet de faire un bilan des forces exercées sur le ver, en admettant que celles-ci sont visqueuses. On montre ainsi que les coefficients de friction transverse et longitudinale peuvent être assimilés à ceux d'un ellipsoïde allongé. Dans le cas du mode reptation, on observe une diminution de l'amplitude de la tête vers la queue. L'interaction ver-substrat est abordée d'abord théoriquement (hypothèse de lubrification). Il en résulte des prédictions pour les coefficients de friction en désaccord avec les résultats expérimentaux. Ce désaccord est expliqué par la mise en évidence de seuils de friction statique. On mesure aussi la rigidité passive d'un ver. Un confinement vertical du ver en milieu liquide permet d'observer une transition continue de la nage vers la reptation. On montre que la période ainsi que le déphasage entre les mouvements de la tête et la queue augmentent avec le placage. Un confinement horizontal du ver sur substrat permet de contraindre l'amplitude. On montre que la longueur d'onde diminue avec l'amplitude
This study on the locomotion of C. Elegans aims at a better understanding of its nervous system and at giving birth to news ideas concerning the conception of new biometics models or objects. We first gave a description of the worm, of its physiology, and of its main modes of locomotion, that is to say the swimming - in liquid medium, and the crawling - on gel substract. When swimming, we analyzed how the dissymmetry pf the movement is necessary for the worm to move on when in viscous medium. Thanks to the analysis of the velocity of the local displacements and by supposing that the forces are viscous, we balanced the forces. We thus demonstrated that transversal and longitudinal friction coefficients could be compared to the coefficients obtained theoretically from an oblong ellipsoïd. When crawling, we were able to observe a diminution of the amplitude from the head to the tail. We first studied the worm-substract interaction theorically - lubrification hypothesis, but the friction coefficients predicted were in contradiction with experimental results. This difference, according to our experiments, was due to static friction. We also measured the rigidity of the worm. By confining the worm vertically in liquid medium, we observed a continuous transition from swimming to — crawling. We proved that the movement of the tail, in comparison with the movement of the head, was more and more delayed as the confinement increased. In these conditions, the global movement of the worm got slower. On substract, we were able to constrain the amplitude thanks to a horizontal confinement; we observed that wavelength decreased with amplitude

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
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

L'étude des systèmes vivants est notoirement difficile. La complexité déconcertante des systèmes biologiques, souvent citée, est principalement due à la complexité de leurs interactions, à leurs multiples niveaux d'organisation et à leur nature dynamique. Dans la quête de compréhension de cette complexité, les parallèles établis avec la physique standard - en particulier la physique statistique - sont à la fois utiles et d'une utilité limitée. D'une part, ils fournissent un riche ensemble d'éléments théoriques et méthodologiques pour construire des théories et concevoir des expériences. D'autre part, la vie biologique se déroule aussi selon des principes qui sont sans équivalent dans la physique de la matière conventionnelle. Une différence cruciale réside dans la notion de fonction : les systèmes biologiques sont façonnés par la nécessité d'accomplir des tâches spécifiques. Un problème général pour les systèmes vivants est de trouver et de promouvoir les configurations qui produisent des fonctions améliorées ou optimales, ce que nous appelons le problème de l'exploration-exploitation (EE). Un exemple spécifique de ce problème se trouve dans la biologie évolutive. Dans ce cas, des mutations génétiques aléatoires soutiennent l'exploration de l'espace de configuration, celles qui correspondent à un succès reproductif plus élevé étant favorisées par la sélection naturelle. Inspirés par ce dernier cas, nous développons un nouveau formalisme qui encode une dynamique générale d'exploration-exploitation pour les réseaux biologiques, représentée comme une exploration d'un paysage fonctionnel. En particulier, notre dynamique d'EE consiste en des changements de configuration stochastiques combinés à l'optimisation dépendante de l'état d'une fonction objective (métrique F). Nous commençons par étudier ses principales caractéristiques à travers l'étude de paysages fonctionnels simples et analytiquement traitables. Nous déployons des simulations pour des applications plus générales et plus complexes. Nous nous penchons ensuite sur le problème du câblage du cerveau, c'est-à-dire le développement du système nerveux d'un individu tout au long de sa vie. Nous soutenons que ce dernier est un autre exemple spécifique du problème de l'EE et qu'il peut donc être traité à l'aide de notre cadre théorique. En particulier, nous nous concentrons sur la maturation du cerveau chez le nématode C. elegans, le seul organisme pour lequel un réseau complet de neurones et de connexions neuronales a été reconstruit, à plusieurs moments du développement. Nous fixons le réseau à la naissance et utilisons le stade adulte pour déduire (i) une description max.ent. parcimonieuse (ERG) de la métrique F pour le cerveau du ver et (ii) les deux paramètres de notre dynamique EE. Selon la topographie de son paysage fonctionnel, le cerveau adulte est caractérisé par une tendance à former des triades et des nœuds de degré supérieur. Nous montrons que notre dynamique d'EE dans un tel paysage est capable de retracer toute l'histoire du développement. En particulier, nous montrons que la trajectoire que nous obtenons reproduit étroitement les autres points temporels expérimentaux que nous n'avons pas utilisés pour l'inférence. Ceci est vrai à la fois dans l'espace des statistiques du modèle et pour un certain nombre d'autres propriétés du réseau. En outre, nous discutons d'une interprétation micro-niveau de la dynamique de l'EE en termes de processus sous-jacent de formation des synapses. Notre étude est un premier pas vers la compréhension au niveau du système du développement d'un cerveau naturel et peut être étendue (i) à des paysages fonctionnels plus complexes, (ii) à d'autres organismes que le C. elegans et (iii) à d'autres problèmes que le câblage du cerveau. En effet, nous pensons que le paradigme de l'exploration-exploitation fait partie de ces principes spécifiques à la vie que nous commençons à peine à découvrir
The study of living systems is notoriously challenging. The often-quoted daunting complexity of biological systems is primarily due to the intricacies of their interactions, their multiple organisation levels and their dynamic nature. In the quest to understand this complexity, parallels drawn with standard physics – in particular, statistical physics -- are both useful and of limited use. On the one hand, they provide a rich set of theoretical and methodological building blocks for constructing theories and designing experiments. On the other hand, life also unfolds according to principles that are unparalleled in the physics of conventional matter. A crucial difference lies in the notion of function: biological systems are shaped by the need to perform specific tasks. A general problem for living systems is to find and promote those configurations that yield improved or optimal functions, we call this the exploration-exploitation (EE) problem. One specific instance of the above is found in evolutionary biology. There, random genetic mutations sustain the exploration of the configuration space, with those leading to higher reproductive success being favoured by natural selection. Inspired by the latter, we develop a novel formalism that encodes a general exploration-exploitation dynamics for biological networks. In particular, our EE dynamics is represented as an exploration of a functional landscape and consists of stochastic configuration changes combined with the state-dependent optimisation of an objective function (F metric). We begin by investigating its main features through the study of simple, analytically tractable functional landscapes. We deploy simulations for more general and complex applications. We then turn to the brain wiring problem, i.e., the development of an individual's nervous system during its early life. We argue that this is another specific instance of the EE problem and therefore can be addressed by using our theoretical framework. In particular, we focus on brain maturation in the nematode C.elegans, the only organism for which a complete network of neurons and neuronal connections has been reconstructed, at multiple developmental time points (seven). We fix the network at birth and use the adult stage to infer (i) a parsimonious maxent (ERG) description of the F metric for the worm brain and (ii) the two parameters of our EE dynamics. According to the topography of its functional landscape, the adult brain is characterised by a tendency to form both triads and high degree nodes. We demonstrate that our EE dynamics in such landscape is capable of tracking down the entire developmental history. In particular, we show that the trajectory we obtain closely reproduces the other experimental time points that we did not use for inference. This is true both in the space of model statistics and for a number of other network properties. Additionally, we discuss a micro-level interpretation of the EE dynamics in terms of the underlying synapse formation process. Our study is a first step towards the system-level understanding of the development of a natural brain and can be extended (i) to encompass more complex functional landscapes, (ii) to different organisms than the C. elegans and (iii) to several different problems than the brain wiring. Indeed, we posit that the exploration-exploitation paradigm is among those life-specific principles that we are just beginning to uncover

Invertebrates have proven to be extremely useful models for gaining insights into the neural and molecular mechanisms of sensory processing, motor control, and higher functions, such as feeding behavior, learning and memory, navigation, and social behavior. Their enormous contribution to neuroscience is due, in part, to the relative simplicity of invertebrate nervous systems and, in part, to the large cells found in some invertebrates, like mollusks. Because of the organizms’ cell size, individual neurons can be surgically removed and assayed for expression of membrane channels, levels of second messengers, protein phosphorylation, and RNA and protein synthesis. Moreover, peptides and nucleotides can be injected into individual neurons. Other invertebrate systems such as Drosophila and Caenorhabditis elegans are ideal models for genetic approaches to the exploration of neuronal function and the neuronal bases of behavior. The Oxford Handbook of Invertebrate Neurobiology reviews neurobiological phenomena, including motor pattern generation, mechanisms of synaptic transmission, and learning and memory, as well as circadian rhythms, development, regeneration, and reproduction. Species-specific behaviors are covered in chapters on the control of swimming in annelids, crustacea, and mollusks; locomotion in hexapods; and camouflage in cephalopods. A unique feature of the handbook is the coverage of social behavior and intentionality in invertebrates. These developments are contextualized in a chapter summarizing past contributions of invertebrate research as well as areas for future studies that will continue to advance the field.

A wiring diagram of the Caenorhabditis elegans nervous system was constructed from serial-section electron micrographs 30 years ago. This wiring diagram divides the 302 neurons in the nervous system of the adult hermaphrodite into three overall classes: sensory neurons, motor neurons that form neuromuscular junctions, and interneurons that connect sensory neurons with motor neurons. Most sensory neurons and interneurons belong to bilaterally symmetric pairs with similar connections and morphologies, while motor neurons belong to larger classes. The C. elegans nervous system presents an exceptional situation in which neuroanatomical connections are extremely well defined and reproducible among animals. These detailed anatomical studies and a parallel genetic attack have increasingly been joined by functional and electrophysiological characterization.

Abstract Sydney Brenner initiated the study of the nematode Caenorhabditis elegans in the early 1960s with the specific intent of developing the organism as a model to study the nervous system. Primarily through the isolation and characterization of mutants that disrupt the functioning of the nervous system at the behavioural level, studies of the nematode have contributed to our understanding of the molecular mechanisms underlying a wide variety of neuronal processes including axonal outgrowth (1), sensory reception (2, 3), and synaptic transmission (4). The strength of the nematode as a model organism is undoubtedly the ability to apply powerful genetics to a biological problem. However, in the long-term, the dissection of the role of molecules in a complex process such as synaptic transmission requires the synthesis of results obtained using a variety of experimental approaches. Here, I first review the approaches available in C. elegans which have been utilized to characterize the molecules underlying the regulated release of neurotransmitter. Subsequently, I examine the complexity of the synaptic transmission apparatus in C. elegans through a discussion of mutants in a variety of genes which perturb the process. Finally, I discuss the avenues of research where the study of C. elegans is most likely to provide future insight that is applicable to understanding the machinery operating at synapses in all organisms.

Abstract Caenorhabditis elegans has a small genome (1 3). At 97 megabases (Mb) it is one thirtieth the size of the human (and other mammalian) genomes. Since C. elegans is a metazoan, its genome might be expected to be significantly more complex than those of single celled eukaryotes such as yeasts and protozoa, yet it is only three times the size of the malaria genome and eight times that of fission yeast. Within this relatively small gene set lie all the instructions for the development and functioning of a fully differentiated animal. These include genes for developmental regulation and embryogenesis, the functioning of complex organ systems, and the integration of the nervous system to control behaviour (4 8). At the inception of the C. elegans genome project, the idea of determining the complete sequence (never mind the structure) of such a vast genome was nearly unthinkable. Thanks to the vision, drive, and sheer hard work of a core group of researchers (in particular John Sulston, Alan Coulson, and Bob Waterston), the dream of having a fully mapped, and fully sequenced genome is complete. The genome project has been central to the success of C. elegans as a model organism, as it allows researchers to home in on the molecular basis of observed genetic defects without having to spend years in the forest of conventional, mapless cloning projects (9). The genome sequence yields the ultimate in genotyping and is the basis on which the next generation of ‘post genomics ‘ research will be based. In addition, the finding of a potential homologue of a gene of interest in the C. elegans genome sequence dataset is often the first inkling a researcher will have that this small nematode might be of interest to them.

Abstract While most animals have a central nervous system (CNS), the process of neurulation, in which neural folding and fusion create a closed neural tube (reviewed in Chapter 2), occurs only in higher vertebrates. Embryos with an abnormal open neural tube are seen, therefore, only in higher animals, including amphibians, birds, and mammals. This fact has precluded advances in our understanding of the genetic basis of neural tube defects (NTDs) from studies of lower organisms. Genetic studies in the fruit fly Drosophila, and in the nematode worm Caenorhabditis elegans, have unraveled the mechanisms underlying many developmental events, including the specification, differentiation, and programmed death of CNS neurons (Ellis and Horvitz, 1986; Gaiano and Fishell, 2002). In contrast, invertebrate studies have not contributed directly to an understanding of the morphogenetic process of neurulation or the molecular basis of NTDs.

In the last few decades, the attention of researchers has been attracted by endogenous FMRFamide-like neuropeptides found in a number of invertebrates, including species of the Nematoda phylum. A foreign literature review was presented for the functional significance of endogenous FMRFamide-like neuropeptides in locomotor behaviour of root-knot phytonematodes, representatives of the genus Meloidogyne Goldi, 1982, namely, Meloidogyne incognita, M. minor, M. hapla and M. graminicola. In Russia, such studies are not carried out. The main characteristics of phytoparasitic neuropeptides were obtained from the study of genes (flp-genes) that encode these neuropeptides. M. incognita was found to have FMRFamidelike positive immunoreactivity in the central nervous system and 19 flp genes. The Mi-flp-12 and Mi-flp-14 genes encode neuropeptides that stimulate locomotor behaviour, while Mi-flp-32 encodes a neuropeptide that inhibits parasite locomotor behaviour. Nematodes M. incognita and M. hapla were found to have G-proteincoupled receptors (GPCRs) encoded by the flp-32 gene, and their similarity to receptor 1 (C26F1) of the free-living nematode Caenorhabditis elegans was detected. Similar data were presented in the literature for M. graminicola. The peptidergic signaling nervous system of root-knot phytonematodes is similar to the system of nematodes in vertebrates and free-living nematodes, which indicates the conservatism of the system in species of the entire Nematoda phylum.