scholarly journals Temporal transitions in post-mitotic neurons throughout the C. elegans nervous system

2020 ◽  
Author(s):  
HaoSheng Sun ◽  
Oliver Hobert
Keyword(s):  
Nervous System ◽  
Transcription Factor ◽  
Embryonic Development ◽  
Model Organism ◽  
Specific Gene ◽  
Molecular Changes ◽  
Functional Changes ◽  
C Elegans ◽  
Larval Stages ◽  
Regulatory Strategies

SUMMARYIn most animals, the majority of the nervous system is generated and assembled into neuronal circuits during embryonic development. However, during juvenile stages, nervous systems still undergo extensive anatomical and functional changes to eventually form a fully mature nervous system by the adult stage. The molecular changes in post-mitotic neurons across post-embryonic development and the genetic programs that control these temporal transitions are not well understood. Using the model organism C. elegans, we comprehensively characterized the distinct functional states (locomotor behavior) and corresponding distinct molecular states (transcriptome) of the post-mitotic nervous system across temporal transitions from early post-embryonic periods to adulthood. We observed pervasive changes in gene expression, many of which are controlled by the developmental upregulation of the conserved heterochronic miRNA lin-4/mir-125 and the subsequent promotion of a mature neuronal transcriptional program through the repression of its target, the transcription factor lin-14. The functional relevance of these molecular transitions are exemplified by a temporally regulated target gene of the lin-14 transcription factor, nlp-45, a neuropeptide-encoding gene. We found that nlp-45 is required for temporal transitions in exploratory activity across larval stages, across sexual maturation, and into a diapause arrest stage. Our studies provide new insights into regulatory strategies that control neuron-type specific gene batteries to modulate distinct behaviors states across temporal, sex and environmental dimensions of post-embryonic development, and also provides a rich atlas of post-embryonic molecular changes to uncover additional regulatory mechanisms.

Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

1996 ◽  
Vol 85 (4) ◽  
pp. 901-912 ◽  
Author(s):  
Michael C. Crowder ◽  
Laynie D. Shebester ◽  
Tim Schedl
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Time Course ◽  
Model Organism ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Effective Concentration ◽  
Forward Genetics ◽  
C Elegans ◽  
Median Effective Concentration

Background The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans. Methods The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C. Results The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations. Conclusions Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.

scholarly journals The homeodomain transcription factor Orthopedia is involved in development of the Drosophila hindgut

Hereditas ◽  
2020 ◽  
Vol 157 (1) ◽  
Author(s):  
Kirsten Hildebrandt ◽  
Nicole Bach ◽  
Dieter Kolb ◽  
Uwe Walldorf
Keyword(s):  
Stem Cells ◽  
Functional Analysis ◽  
Nervous System ◽  
Transcription Factor ◽  
Embryonic Development ◽  
Gene Targeting ◽  
Homeobox Gene ◽  
Genetic Screen ◽  
Specific Form ◽  
Transcriptional Activators

Abstract Background The Drosophila hindgut is commonly used model for studying various aspects of organogenesis like primordium establishment, further specification, patterning, and morphogenesis. During embryonic development of Drosophila, many transcriptional activators are involved in the formation of the hindgut. The transcription factor Orthopedia (Otp), a member of the 57B homeobox gene cluster, is expressed in the hindgut and nervous system of developing Drosophila embryos, but due to the lack of mutants no functional analysis has been conducted yet. Results We show that two different otp transcripts, a hindgut-specific and a nervous system-specific form, are present in the Drosophila embryo. Using an Otp antibody, a detailed expression analysis during hindgut development was carried out. Otp was not only expressed in the embryonic hindgut, but also in the larval and adult hindgut. To analyse the function of otp, we generated the mutant otp allele otpGT by ends-out gene targeting. In addition, we isolated two EMS-induced otp alleles in a genetic screen for mutants of the 57B region. All three otp alleles showed embryonic lethality with a severe hindgut phenotype. Anal pads were reduced and the large intestine was completely missing. This phenotype is due to apoptosis in the hindgut primordium and the developing hindgut. Conclusion Our data suggest that Otp is another important factor for hindgut development of Drosophila. As a downstream factor of byn Otp is most likely present only in differentiated hindgut cells during all stages of development rather than in stem cells.

scholarly journals Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans

2016 ◽  
Author(s):  
Aaron C. Daugherty ◽  
Robin Yeo ◽  
Jason D. Buenrostro ◽  
William J. Greenleaf ◽  
Anshul Kundaje ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Developmental Stages ◽  
Model Organism ◽  
High Sensitivity ◽  
Chromatin Accessibility ◽  
Chromatin Dynamics ◽  
C Elegans ◽  
Crucial Component ◽  
Organismal Development

AbstractChromatin accessibility, a crucial component of genome regulation, has primarily been studied in homogeneous and simple systems, such as isolated cell populations or early-development models. Whether chromatin accessibility can be assessed in complex, dynamic systems in vivo with high sensitivity remains largely unexplored. In this study, we use ATAC-seq to identify chromatin accessibility changes in a whole animal, the model organism C. elegans, from embryogenesis to adulthood. Chromatin accessibility changes between developmental stages are highly reproducible, recapitulate histone modification changes, and reveal key regulatory aspects of the epigenomic landscape throughout organismal development. We find that over 5,000 distal non-coding regions exhibit dynamic changes in chromatin accessibility between developmental stages, and could thereby represent putative enhancers. When tested in vivo, several of these putative enhancers indeed drive novel cell-type-and temporal-specific patterns of expression. Finally, by integrating transcription factor binding motifs in a machine learning framework, we identify EOR-1 as a unique transcription factor that may regulate chromatin dynamics during development. Our study provides a unique resource for C. elegans, a system in which the prevalence and importance of enhancers remains poorly characterized, and demonstrates the power of using whole organism chromatin accessibility to identify novel regulatory regions in complex systems.

scholarly journals In silico analysis of the transcriptional regulatory logic of neuronal identity specification throughout the C. elegans nervous system

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Lori Glenwinkel ◽  
Seth R Taylor ◽  
Kasper Langebeck-Jensen ◽  
Laura Pereira ◽  
Molly B Reilly ◽  
...  
Keyword(s):  
Nervous System ◽  
Transcription Factors ◽  
Single Cell ◽  
Expression Profiles ◽  
Neuronal Cell ◽  
In Silico Analysis ◽  
Specific Gene ◽  
Neuron Type ◽  
C Elegans ◽  
Neuronal Identity

The generation of the enormous diversity of neuronal cell types in a differentiating nervous system entails the activation of neuron type-specific gene batteries. To examine the regulatory logic that controls the expression of neuron type-specific gene batteries, we interrogate single cell expression profiles of all 118 neuron classes of the Caenorhabditis elegans nervous system for the presence of DNA binding motifs of 136 neuronally expressed C. elegans transcription factors. Using a phylogenetic footprinting pipeline, we identify cis-regulatory motif enrichments among neuron class-specific gene batteries and we identify cognate transcription factors for 117 of the 118 neuron classes. In addition to predicting novel regulators of neuronal identities, our nervous system-wide analysis at single cell resolution supports the hypothesis that many transcription factors directly co-regulate the cohort of effector genes that define a neuron type, thereby corroborating the concept of so-called terminal selectors of neuronal identity. Our analysis provides a blueprint for how individual components of an entire nervous system are genetically specified.

Multiple Roles of RNA Regulatory Factors in Neuronal Development and Function in C. elegans

2020 ◽  
Author(s):  
Matthew G. Andrusiak ◽  
Yishi Jin
Keyword(s):  
Nervous System ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Model Organism ◽  
Nervous System Development ◽  
Forward Genetics ◽  
C Elegans

Recent evidence has highlighted the dynamic nature of mRNA regulation, particularly in the nervous system, from complex pre-mRNA processing to long-range transport and long-term storage of mature mRNAs. In accordance with the importance for mRNA-mediated regulation of nervous system development and maintenance, various mutations in RNA-binding proteins are associated with a range of human disorders. C. elegans express many RNA-binding factors that have human orthologs and perform similar biochemical functions. This chapter focuses on the research using C. elegans to dissect molecular mechanisms involving mRNA-mediated pathways. It highlights the key approaches and findings that integrate genetic and genomic studies in the nervous system. The analyses of genetic mutants, primarily using forward genetics, offer functional insights for genes important for neuronal development, synaptic transmission, and neuronal repair. In combination with single-neuron cell biology and cell-type genomics, the knowledge learned from this model organism has continued to lead to ground-breaking discoveries.

scholarly journals The Emergent Connectome in Caenorhabditis elegans Embryogenesis

2017 ◽  
Author(s):  
◽  
Bradly Alicea
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Cell Lineage ◽  
Model Organism ◽  
Secondary Data ◽  
Building Blocks ◽  
C Elegans ◽  
Differentiated Cells ◽  
Adult Hermaphrodite ◽  
Nervous System Function

ABSTRACTThe relatively new field of connectomics provides us with a unique window into nervous system function. In the model organism Caenorhabditis elegans, this promise is even greater due to the relatively small number of cells (302) in its nervous system. While the adult C. elegans connectome has been characterized, the emergence of these networks in development has yet to be established. In this paper, we approach this problem using secondary data describing the birth times of terminally-differentiated cells as they appear in the embryo and a connectomics model for nervous system cells in the adult hermaphrodite. By combining these two sources of data, we can better understand patterns that emerge in an incipient connectome. This includes identifying at what point in embryogenesis the cells of a connectome first comes into being, potentially observing some of the earliest neuron-neuron interactions, and making comparisons between the formally-defined connectome and developmental cell lineages. An analysis is also conducted to root terminally-differentiated cells in their developmental cell lineage precursors. This reveals subnetworks with different properties at 300 minutes of embryogenesis. Additional investigations reveal the spatial position of neuronal cells born during pre-hatch development, both within and outside the connectome model, in the context of all developmental cells in the embryo. Overall, these analyses reveal important information about the birth order of specific cells in the connectome, key building blocks of global connectivity, and how these structures correspond to key events in early development.

scholarly journals Visualizing the organization and differentiation of the male-specific nervous system of C. elegans

2021 ◽  
Author(s):  
Tessa Tekieli ◽  
Eviatar Yemini ◽  
Amin Nejatbakhsh ◽  
Erdem Varol ◽  
Robert W Fernandez ◽  
...  
Keyword(s):  
Nervous System ◽  
Just In Time ◽  
Differentiation Markers ◽  
C Elegans ◽  
Larval Stages ◽  
Fourth Larval Stage ◽  
Developmental Patterning ◽  
Male Specific ◽  
Cluster Gene ◽  
The Brain

Sex differences in the brain are prevalent throughout the animal kingdom and particularly well appreciated in the nematode C. elegans. While 294 neurons are shared between the two sexes, the nervous system of the male contains an additional 93 male-specific neurons, most of which have received very little attention so far. To make these neurons amenable for future study, we describe here how a multicolor, multipromoter reporter transgene, NeuroPAL, is capable of visualizing the distinct identities of all male specific neurons. We used this tool to visualize and characterize a number of features of the male-specific nervous system. We provide several proofs of concept for using NeuroPAL to identify the sites of expression of gfp-tagged reporter genes. We demonstrate the usage of NeuroPAL for cellular fate analysis by analyzing the effect of removal of developmental patterning genes, including a HOX cluster gene (egl-5), a miRNA (lin-4) and a proneural gene (lin-32/Ato), on neuronal identity acquisition within the male-specific nervous system. We use NeuroPAL and its intrinsic cohort of more than 40 distinct differentiation markers to show that, even though male-specific neurons are generated throughout all four larval stages, they execute their terminal differentiation program in a coordinated manner in the fourth larval stage that is concomitant with male tale retraction. This wave of differentiation couples neuronal maturation programs with the appearance of sexual organs. We call this wave 'just-in-time' differentiation by its analogy to the mechanism of 'just-in-time' transcription of metabolic pathway genes.

scholarly journals Expression profiling of the mature C. elegans nervous system by single-cell RNA-Sequencing

2019 ◽  
Author(s):  
Seth R Taylor ◽  
Gabriel Santpere ◽  
Molly Reilly ◽  
Lori Glenwinkel ◽  
Abigail Poff ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Single Cell ◽  
Web Application ◽  
Model Organism ◽  
Structural Motif ◽  
Individual Neuron ◽  
C Elegans ◽  
Link Type ◽  
The Individual

AbstractA single neuron and its synapses define the fundamental structural motif of the brain but the underlying gene expression programs that specify individual neuron types are poorly understood. To address this question in a model organism, we have produced a gene expression profile of >90% of the individual neuron classes in the C. elegans nervous system, an ensemble of neurons for which both the anatomy and connectivity are uniquely defined at single cell resolution. We generated single cell transcriptomes for 52,412 neurons that resolve as clusters corresponding to 109 of the canonical 118 neuron classes in the mature hermaphrodite nervous system. Detailed analysis revealed molecular signatures that further subdivide identified classes into specific neuronal subtypes. Notably, neuropeptide-related genes are often differentially expressed between subtypes of the given neuron class which points to distinct functional characteristics. All of these data are publicly available at our website (http://www.cengen.org) and can be interrogated at the web application SCeNGEA (https://cengen.shinyapps.io/SCeNGEA). We expect that this gene expression catalog will spur the goal of delineating the underlying mechanisms that define the developmental lineage, detailed anatomy, synaptic connectivity and function of each type of C. elegans neuron.

scholarly journals Molecular topography of an entire nervous system

2020 ◽  
Author(s):  
Seth R Taylor ◽  
Gabriel Santpere ◽  
Alexis Weinreb ◽  
Alec Barrett ◽  
Molly B. Reilly ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Web Application ◽  
Gene Families ◽  
Regulatory Elements ◽  
Individual Neuron ◽  
Specific Gene ◽  
C Elegans ◽  
Underlying Mechanisms ◽  
And Function

SummaryNervous systems are constructed from a deep repertoire of neuron types but the underlying gene expression programs that specify individual neuron identities are poorly understood. To address this deficit, we have produced an expression profile of all 302 neurons of the C. elegans nervous system that matches the single cell resolution of its anatomy and wiring diagram. Our results suggest that individual neuron classes can be solely identified by combinatorial expression of specific gene families. For example, each neuron class expresses unique codes of ∼23 neuropeptide-encoding genes and ∼36 neuropeptide receptors thus pointing to an expansive “wireless” signaling network. To demonstrate the utility of this uniquely comprehensive gene expression catalog, we used computational approaches to (1) identify cis-regulatory elements for neuron-specific gene expression across the nervous system and (2) reveal adhesion proteins with potential roles in synaptic specificity and process placement. These data are available at cengen.org and can be interrogated at the web application CengenApp. We expect that this neuron-specific directory of gene expression will spur investigations of underlying mechanisms that define anatomy, connectivity and function throughout the C. elegans nervous system.

scholarly journals Identification of essential genes in Caenorhabditis elegans through whole genome sequencing of legacy mutant collections

2021 ◽  
Author(s):  
Donald G. Moerman ◽  
Erica Li-Leger ◽  
Stephane Flibotte ◽  
Ralf Schnabel ◽  
Heinke Holzkamp ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Functional Characterization ◽  
Model Organism ◽  
Essential Genes ◽  
Whole Genome ◽  
C Elegans ◽  
Novel Alleles ◽  
Unknown Male

It has been estimated that 15-30% of the ~20,000 genes in C. elegans are essential, yet many of these genes remain to be identified or characterized. With the goal of identifying unknown essential genes, we performed whole genome sequencing on complementation pairs from legacy collections of maternal-effect lethal and sterile mutants. This approach uncovered maternal genes required for embryonic development and genes with putative sperm-specific functions. In total, 58 essential genes were identified on chromosomes III, IV, and V, of which 49 genes are represented by novel alleles in this collection. Of these 49 genes, 19 (40 alleles) were selected for further functional characterization. The terminal phenotypes of embryos were examined, revealing defects in cell division, morphogenesis, and osmotic integrity of the eggshell. Mating assays with wild-type males revealed previously unknown male-expressed genes required for fertilization and embryonic development. The result of this study is a catalogue of mutant alleles in essential genes that will serve as a resource to guide further study toward a more complete understanding of this important model organism. As many genes and developmental pathways in C. elegans are conserved and essential genes are often linked to human disease, uncovering the function of these genes may also provide insight to further our understanding of human biology.

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