The Nematode Caenorhabditis elegans A Model Animal “Made for Microscopy”

The small unassuming nematode, Caenorhabditis elegans is only one millimeter long and lives in the soil munching on bacteria. While many nematode (roundworm) species are parasites with medical or agricultural importance, C. elegans seems to harm no one. Yet, this animal has attained a status in medical science that compares to more complex organisms such as the mouse or fruit fly in its utility for scientific discovery. It has been the subject of thousands of studies dealing with topics as diverse as nutrition, aging, and nervous system development. About 5000 scientists are now pursuing this single species in hundreds of laboratories worldwide. In 2002, the Nobel Prize in Medicine was awarded to three of the pioneers in establishing C. elegans as a “model organism“: Sydney Brenner, John Sulston, and H. Robert Horvitz. Why study worms?Sydney Brenner first turned his attention to C. elegans in the 1960's. Working at the Medical Research Council in England, he was looking for a small animal with inexpensive tastes that could be easily cultured in the laboratory.

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Molecular and Comparative Genetics of Mental Retardation

Genetics ◽

10.1093/genetics/166.2.835 ◽

2004 ◽

Vol 166 (2) ◽

pp. 835-881 ◽

Cited By ~ 2

Author(s):

Jennifer K Inlow ◽

Linda L Restifo

Keyword(s):

Mental Retardation ◽

Homo Sapiens ◽

System Development ◽

Laboratory Data ◽

Fruit Fly ◽

Mendelian Inheritance ◽

Nervous System Development ◽

Skewed Distribution ◽

Therapeutic Drug ◽

Cellular Mechanisms

Abstract Affecting 1-3% of the population, mental retardation (MR) poses significant challenges for clinicians and scientists. Understanding the biology of MR is complicated by the extraordinary heterogeneity of genetic MR disorders. Detailed analyses of >1000 Online Mendelian Inheritance in Man (OMIM) database entries and literature searches through September 2003 revealed 282 molecularly identified MR genes. We estimate that hundreds more MR genes remain to be identified. A novel test, in which we distributed unmapped MR disorders proportionately across the autosomes, failed to eliminate the well-known X-chromosome overrepresentation of MR genes and candidate genes. This evidence argues against ascertainment bias as the main cause of the skewed distribution. On the basis of a synthesis of clinical and laboratory data, we developed a biological functions classification scheme for MR genes. Metabolic pathways, signaling pathways, and transcription are the most common functions, but numerous other aspects of neuronal and glial biology are controlled by MR genes as well. Using protein sequence and domain-organization comparisons, we found a striking conservation of MR genes and genetic pathways across the ∼700 million years that separate Homo sapiens and Drosophila melanogaster. Eighty-seven percent have one or more fruit fly homologs and 76% have at least one candidate functional ortholog. We propose that D. melanogaster can be used in a systematic manner to study MR and possibly to develop bioassays for therapeutic drug discovery. We selected 42 Drosophila orthologs as most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to MR.

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Complex Cooperative Functions of Heparan Sulfate Proteoglycans Shape Nervous System Development in Caenorhabditis elegans

G3 Genes|Genome|Genetics ◽

10.1534/g3.114.012591 ◽

2014 ◽

Vol 4 (10) ◽

pp. 1859-1870 ◽

Cited By ~ 20

Author(s):

Carlos A. Díaz-Balzac ◽

María I. Lázaro-Peña ◽

Eillen Tecle ◽

Nathali Gomez ◽

Hannes E. Bülow

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Heparan Sulfate ◽

System Development ◽

Nervous System Development ◽

Heparan Sulfate Proteoglycans

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Exploring Caenorhabditis elegans Behavior: An Inquiry-Based Laboratory Module for Middle or High School Students

The American Biology Teacher ◽

10.1525/abt.2017.79.8.661 ◽

2017 ◽

Vol 79 (8) ◽

pp. 661-667

Author(s):

Sarah N. Deffit ◽

Cori Neff ◽

Jennifer R. Kowalski

Keyword(s):

High School ◽

High School Students ◽

Caenorhabditis Elegans ◽

Scientific Inquiry ◽

Scientific Discovery ◽

Model Organism ◽

School Students ◽

Laboratory Activity ◽

Research Questions ◽

Students Attitudes

The use of primary scientific inquiry and experimentation to develop students’ understanding of methodologies used by scientists and the nature of science is a key component of the Next-Generation Science Standards (NGSS). Introduction to inquiry-based experimentation also has been shown to improve students’ attitudes and interest in science. However, implementing scientific inquiry activities that include experimental design and data analysis in a classroom of middle or high school students can be daunting for teachers with limited experimental experience. Here, we present a four- to five-day, inquiry-based laboratory activity designed to teach students about the scientific process and excite them about scientific discovery while providing opportunities for interactions of both teachers and students with scientists in the field. Within this laboratory module, students make observations and develop their own research questions, then design, execute, analyze, and present the results of their hypothesis-driven experiments investigating the behavior of Caenorhabditis elegans, a relatively inexpensive and tractable model organism. Our experience running this module in a middle school biology classroom suggests students enjoyed the opportunity to investigate their own research questions, and post-course surveys indicated that students’ fear of biology decreased and their interest in biology-related careers increased following participation in the module.

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ngn-1/neurogenin Activates Transcription of Multiple Terminal Selector Transcription Factors in the Caenorhabditis elegans Nervous System

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401126 ◽

2020 ◽

Vol 10 (6) ◽

pp. 1949-1962 ◽

Cited By ~ 1

Author(s):

Elyse L. Christensen ◽

Alexandra Beasley ◽

Jessica Radchuk ◽

Zachery E. Mielko ◽

Elicia Preston ◽

...

Keyword(s):

Nervous System ◽

Transcription Factors ◽

Caenorhabditis Elegans ◽

Cell Fate ◽

Neural Development ◽

System Development ◽

Neuronal Cell ◽

Nervous System Development ◽

Link Type ◽

Neuroblast Migration

Proper nervous system development is required for an organism’s survival and function. Defects in neurogenesis have been linked to neurodevelopmental disorders such as schizophrenia and autism. Understanding the gene regulatory networks that orchestrate neural development, specifically cascades of proneural transcription factors, can better elucidate which genes are most important during early neurogenesis. Neurogenins are a family of deeply conserved factors shown to be both necessary and sufficient for the development of neural subtypes. However, the immediate downstream targets of neurogenin are not well characterized. The objective of this study was to further elucidate the role of ngn-1/neurogenin in nervous system development and to identify its downstream transcriptional targets, using the nematode Caenorhabditis elegans as a model for this work. We found that ngn-1 is required for axon outgrowth, nerve ring architecture, and neuronal cell fate specification. We also showed that ngn-1 may have roles in neuroblast migration and epithelial integrity during embryonic development. Using RNA sequencing and comparative transcriptome analysis, we identified eight transcription factors (hlh-34/NPAS1, unc-42/PROP1, ceh-17/PHOX2A, lim-4/LHX6, fax-1/NR2E3, lin-11/LHX1, tlp-1/ZNF503, and nhr-23/RORB) whose transcription is activated, either directly or indirectly, by ngn-1. Our results show that ngn-1 has a role in transcribing known terminal regulators that establish and maintain cell fate of differentiated neural subtypes and confirms that ngn-1 functions as a proneural transcription factor in C. elegans neurogenesis.

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Regulation of Gliogenesis by lin-32/Atoh1 in Caenorhabditis elegans

G3 Genes|Genome|Genetics ◽

10.1534/g3.120.401547 ◽

2020 ◽

Vol 10 (9) ◽

pp. 3271-3278 ◽

Cited By ~ 2

Author(s):

Albert Zhang ◽

Kentaro Noma ◽

Dong Yan

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Embryonic Development ◽

Molecular Mechanisms ◽

System Development ◽

Nervous System Development ◽

Proneural Gene ◽

C Elegans ◽

Fundamental Process ◽

Mutant Phenotypes

Abstract The regulation of gliogenesis is a fundamental process for nervous system development, as the appropriate glial number and identity is required for a functional nervous system. To investigate the molecular mechanisms involved in gliogenesis, we used C. elegans as a model and identified the function of the proneural gene lin-32/Atoh1 in gliogenesis. We found that lin-32 functions during embryonic development to negatively regulate the number of AMsh glia. The ectopic AMsh cells at least partially arise from cells originally fated to become CEPsh glia, suggesting that lin-32 is involved in the specification of specific glial subtypes. Moreover, we show that lin-32 acts in parallel with cnd-1/ NeuroD1 and ngn-1/ Neurog1 in negatively regulating an AMsh glia fate. Furthermore, expression of murine Atoh1 fully rescues lin-32 mutant phenotypes, suggesting lin-32/Atoh1 may have a conserved role in glial specification.

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No pun intended: future directions in invertebrate glial cell migration studies

Neuron Glia Biology ◽

10.1017/s1740925x07000634 ◽

2007 ◽

Vol 3 (1) ◽

pp. 45-54 ◽

Cited By ~ 4

Author(s):

Patrick Cafferty ◽

Vanessa J. Auld

Keyword(s):

Nervous System ◽

Cell Migration ◽

Glial Cell ◽

Glial Cells ◽

Molecular Mechanisms ◽

System Development ◽

Fruit Fly ◽

Nervous System Development ◽

Wide Range ◽

And Function

AbstractGlial cells play a wide range of essential roles in both nervous system development and function and has been reviewed recently (Parker and Auld, 2006). Glia provide an insulating sheath, either form or direct the formation of the blood–brain barrier, contribute to ion and metabolite homeostasis and provide guidance cues. Glial function often depends on the ability of glial cells to migrate toward specific locations during nervous system development. Work in nervous system development in insects, in particular in the fruit fly Drosophila melanogaster and the tobacco hornworm Manduca sexta, has provided significant insight into the roles of glia, although the molecular mechanisms underlying glial cell migration are being determined only now. Indeed, many of the processes and mechanisms discovered in these simpler systems have direct parallels in the development of vertebrate nervous systems. In this review, we first examine the developmental contexts in which invertebrate glial cell migration has been observed, we next discuss the characterized molecules required for proper glial cell migration, and we finally discuss future goals to be addressed in the study of glial cell development.

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Long-term impact of intensive postgraduate laboratory training at the Cold Spring Harbor Neurobiology of Drosophila summer course

10.1101/369892 ◽

2018 ◽

Author(s):

Sarah Ly ◽

Karla Kaun ◽

Chi-Hon Lee ◽

David Stewart ◽

Stefan R. Pulver ◽

...

Keyword(s):

System Development ◽

Model Organism ◽

Nervous System Development ◽

Cold Spring Harbor ◽

Development Activity ◽

Cold Spring ◽

Long Term Impact ◽

High Level ◽

The Impact ◽

Positive Impacts

AbstractIntensive postgraduate courses provide an opportunity for junior and senior level scientists to learn concepts and techniques that will advance their training and research programs. It is commonly assumed that short intensive courses have positive impacts within fields of research; however, these assumptions are rarely tested. Here we describe the framework of a long running postgraduate summer course at Cold Spring Harbor and attempt to quantify the impact made over its history. For over three decades, the Drosophila Neurobiology: Genes, Circuits & Behavior Summer Course at Cold Spring Harbor Laboratories (CSHL) has provided participants with intense instruction on a wide variety of topics and techniques in integrative neuroscience using Drosophila as a model organism. Students are introduced to the latest approaches for studying nervous system development, activity and connectivity, as well as complex behaviors and diseases. The course has a long history of successful alumni, many of whom describe participation in the course as foundational to their training. Student surveys of recent participants indicate a high level of satisfaction, improved career outcomes, and direct impact on publications. Analysis of student success reveals that over 64% of participants obtain independent faculty positions. Further, we describe ongoing efforts to enhance diversity and encourage access to scientific research at undergraduate-focused institutions. Together, our findings suggest that laboratory-intensive postgraduate courses provide a highly effective mechanism for scientific training that has lasting positive impacts on trainees.

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Signaling in glial development: differentiation migration and axon guidance

Biochemistry and Cell Biology ◽

10.1139/o04-119 ◽

2004 ◽

Vol 82 (6) ◽

pp. 694-707 ◽

Cited By ~ 14

Author(s):

Robert J Parker ◽

Vanessa J Auld

Keyword(s):

Nervous System ◽

Axon Guidance ◽

Egf Receptor ◽

System Development ◽

Molecular Genetic ◽

Model Organism ◽

Cell Types ◽

Nervous System Development ◽

Glial Development ◽

Embryonic Nervous System

Glial cells have diverse functions that are necessary for the proper development and function of complex nervous systems. During development, a variety of reciprocal signaling interactions between glia and neurons dictate all parts of nervous system development. Glia may provide attractive, repulsive, or contact-mediated cues to steer neuronal growth cones and ensure that neurons find their appropriate synaptic targets. In fact, both neurons and glia may act as migrational substrates for one another at different times during development. Also, the exchange of trophic signals between glia and neurons is essential for the proper bundling, fasciculation, and ensheathement of axons as well as the differentiation and survival of both cell types. The growing number of links between glial malfunction and human disease has generated great interest in glial biology. Because of its relative simplicity and the many molecular genetic tools available, Drosophila is an excellent model organism for studying glial development. This review will outline the roles of glia and their interactions with neurons in the embryonic nervous system of the fly.Key words: glia, axon guidance, migration, EGF receptor.

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