Article
Multidisciplinary Sciences
Holly K. Gildea, Phillip A. Frankino, Sarah U. Tronnes, Corinne L. Pender, Jenni Durieux, Julian G. Dishart, Hyun Ok Choi, Tayla D. Hunter, Shannon S. Cheung, Ashley E. Frakes, Edward Sukarto, Kevin Wickham, Andrew Dillin
Summary: Aging organisms lose the ability to induce stress responses, making them vulnerable to protein toxicity and tissue damage. Neurons and glial cells can signal to induce protective stress responses in specific organelles. Understanding the role of glial cells in immune function and lifespan extension can provide valuable insights.
Article
Chemistry, Multidisciplinary
Michael R. Harris, Thomas P. Wytock, Istvan A. Kovacs
Summary: The difficulty of mapping synaptic polarity is addressed through computational inference in this study. The researchers use different experimental scenarios, including the integration of gene expression data and a connectome model, to infer synaptic polarities. They introduce a high-performance method that successfully infers a large number of synaptic polarities, contributing to a more realistic understanding of brain models.
Article
Biochemistry & Molecular Biology
Jinrui Xu, Michelle M. Kudron, Alec Victorsen, Jiahao Gao, Haneen N. Ammouri, Fabio C. P. Navarro, Louis Gevirtzman, Robert H. Waterston, Kevin P. White, Valerie Reinke, Mark Gerstein
Summary: Chromatin immunoprecipitation followed by sequencing is the gold standard for detecting transcription-factor binding sites, with success dependent on appropriate controls; while DNA input corrects for uneven sonication, mock IP corrects for nonspecific interactions, especially in complex samples like whole organisms. The two control types perform similarly in cell lines, but mock IP substantially reduces the number of spurious sites in complex samples, ultimately improving binding site detection.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Neurosciences
Jiayang Chen, Mary E. Lambo, Xia Ge, Joshua T. Dearborn, Yating Liu, Katherine B. McCullough, Raylynn G. Swift, Dora R. Tabachnick, Lucy Tian, Kevin Noguchi, Joel R. Garbow, John N. Constantino, Harrison W. Gabel, Keith B. Hengen, Susan E. Maloney, Joseph D. Dougherty
Summary: A new neurodevelopmental syndrome caused by loss-of-function mutations in the MYT1L gene has been defined, with a haploinsufficient mouse model mimicking common clinical phenotypes. Disrupted gene expression and precocious neuronal differentiation were identified as mechanisms for microcephaly during brain development, while failure of transcriptional and chromatin maturation was discovered in adults, resulting in disruptions in baseline physiological properties of neurons. Behavioral anomalies, including hyperactivity, muscle weakness, and social alterations, were observed, with more severe phenotypes in males.
Article
Multidisciplinary Sciences
Dionysia Petratou, Martha Gjikolaj, Eva Kaulich, William Schafer, Nektarios Tavernarakis
Summary: The nervous system plays a crucial role in systemic stress response and maintaining neuronal sodium homeostasis. Imbalance in neuronal sodium homeostasis is linked to nervous system pathologies, but the effects of stress on this balance are not well understood. This study reveals that the DEG/ENaC family member DEL-4 functions as a proton-inactivated sodium channel in neuronal membranes and synapses, modulating locomotion in Caenorhabditis elegans. Heat stress and starvation influence DEL-4 expression, which in turn affects the expression and activity of stress-response transcription factors and leads to appropriate motor adaptations. Additionally, DEL-4 deficiency affects dopaminergic neurons and neurotransmission, while promoting neuronal survival in models of neurodegenerative diseases. These findings provide insights into the molecular mechanisms underlying the role of sodium channels in neuronal function and adaptation during stress.
Article
Multidisciplinary Sciences
Hamilton White, Vanessa Kamara, Veronika Gorski, Molly Busby, Dirk R. Albrecht
Summary: Fluorescent genetically encoded calcium indicators have greatly contributed to our understanding of neural dynamics. However, methods that can assess neural function across many individuals at once are needed. This paper describes the use of wide-field microscopy to scale up neuronal recordings to many small organisms at once, and presents examples of functional changes in neural excitability and dynamics.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Biochemistry & Molecular Biology
Erika da Cruz Guedes, Adolfo Garcia Erustes, Anderson H. F. F. Leao, Cesar Alves Carneiro, Vanessa C. Abilio, Antonio W. Zuardi, Jaime Eduardo C. Hallak, Jose Alexandre Crippa, Claudia Bincoletto, Soraya S. Smaili, Patricia Reckziegel, Gustavo J. S. Pereira
Summary: In this study, the potential neuroprotective effect of cannabidiol (CBD) in the treatment of Parkinson's Disease (PD) was evaluated using a C. elegans model. The results showed that CBD could reverse locomotor alterations induced by reserpine and protect neurons from degeneration. Additionally, CBD also reduced the formation of reactive oxygen species (ROS) and accumulation of alpha-synuclein protein. These findings indicate that CBD acts as a neuroprotector in dopaminergic neurons and highlights its potential in the treatment of PD.
NEUROCHEMICAL RESEARCH
(2023)
Article
Chemistry, Analytical
Anle Ge, Liang Hu, JiaXing Fan, Minghai Ge, Xixian Wang, Shanshan Wang, Xiaojun Feng, Wei Du, Bi-Feng Liu
Summary: The optogenetic method is commonly used to study neuronal function and connectivity in neural circuits. This study presents a portable optofluidic platform using optical fiber illumination for optogenetic manipulation in nematode C. elegans. It allows precise activation of neurons and simultaneous measurement of cellular signals, providing a simple, rapid, and cost-effective strategy for studying neural circuits.
Article
Biochemistry & Molecular Biology
Xueqing Wang, Quanlong Jiang, Yuanyuan Song, Zhidong He, Hongdao Zhang, Mengjiao Song, Xiaona Zhang, Yumin Dai, Oezlem Karalay, Christoph Dieterich, Adam Antebi, Ligang Wu, Jing-Dong J. Han, Yidong Shen
Summary: Ageing is a complex process with different features in different tissues. This study isolated cells from different tissues in worms and analyzed the transcriptomic changes during ageing, revealing the diversity of ageing across tissues and identifying tissue-specific longevity regulators. Additionally, novel factors controlling intestinal barrier integrity and sarcomere structure during ageing were discovered.
Review
Cell Biology
Georgios Konstantinidis, Nektarios Tavernarakis
Summary: Autophagy is an evolutionarily conserved degradation process that helps maintain cell homeostasis and responds to various cellular stress conditions. It plays critical roles in development, maintenance, and survival of different cell populations, including neurons, and a decline in autophagy with age can predispose animals to age-related diseases.
Article
Biology
Thanh Thi Vuong-Brender, Sean Flynn, Yvonne Vallis, Mario de Bono
Summary: CAMTAs are ancient proteins expressed broadly in nervous systems, controlling neuronal CaM levels. Loss of CAMT-1, the sole C. elegans CAMTA, results in behavioral and neuronal Ca2+ signaling defects.
Article
Multidisciplinary Sciences
Phillip A. Frankino, Talha F. Siddiqi, Theodore Bolas, Raz Bar-Ziv, Holly K. Gildea, Hanlin Zhang, Ryo Higuchi-Sanabria, Andrew Dillin
Summary: The transcription factor SKN-1/NRF2 can sense and respond to changes in metabolic state. Knockdown of the amidohydrolase T12A2.1/amdh-1 activates a unique subset of SKN-1 regulated genes, independent of P38-MAPK signaling components. Histidine catabolism genes are required for this activation, possibly through accumulation of a specific catabolite. Activating SKN-1 results in increased oxidative stress resistance but decreased survival to heat stress.
Article
Environmental Sciences
Yunhan Yang, Qiuli Wu, Dayong Wang
Summary: This study identified the roles of neuronal G alpha proteins GOA-1, GSA-1, and GPA-10 in controlling the response to polystyrene nanoparticles in nematodes. These proteins transduce signals from multiple GPCRs to different downstream signaling pathways, regulating toxicity effects. The findings emphasize the significance of GPCRs-G alpha signaling cascade in neurons for managing nanoplastic responses in organisms.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Multidisciplinary Sciences
Jadiel A. Wasson, Gareth Harris, Sabine Keppler-Ross, Trisha J. Brock, Abdul R. Dar, Rebecca A. Butcher, Sylvia E. J. Fischer, Konstantinos Kagias, Jon Clardy, Yun Zhang, Susan E. Mango
Summary: This study reveals that social cues can influence maternal provisioning to offspring in Caenorhabditis elegans through a neuron and neuropeptide. Parental FMRFamide-like peptide signaling affects offspring's oxidative stress resistance and gene silencing, indicating a previously unknown pathway for intergenerational communication. Loss of social cues in the parental environment is shown to stimulate stress responses across generations.
Article
Cell Biology
Shi Quan Wong, Catherine J. Ryan, Dennis M. Bonal, Joslyn Mills, Louis R. Lapierre
Summary: Neuronal TFEB plays an important role in stress resistance and longevity regulation. Its rescue improves heat stress resistance in wildtype animals but not daf-2 mutants. Neuronal TFEB modulates neurotransmission through the uncharacterized protein W06A11.1, inducing peripheral mitochondrial fragmentation and enhancing organismal heat stress resistance.
Article
Biochemistry & Molecular Biology
Eviatar Yemini, Albert Lin, Amin Nejatbakhsh, Erdem Varol, Ruoxi Sun, Gonzalo E. Mena, Aravinthan D. T. Samuel, Liam Paninski, Vivek Venkatachalam, Oliver Hobert
Summary: NeuroPAL is a multicolor transgene that helps resolve neuronal identities in C. elegans. It can be used with various reporters of gene expression or neuronal dynamics and has been utilized in studies related to metabotropic receptor expression, cell fate changes, and brainwide activity in response to chemosensory cues.
Article
Biochemistry & Molecular Biology
Ulkar Aghayeva, Abhishek Bhattacharya, Surojit Sural, Eliza Jaeger, Matthew Churgin, Christopher Fang-Yen, Oliver Hobert
Summary: The study demonstrates the crucial role of transcription factors from 3 different hormonal signaling systems in tissue remodeling during Caenorhabditis elegans entry into the dauer stage. DAF-3/SMAD is required in sensory neurons for promoting and maintaining animal-wide tissue remodeling events while DAF-16/FoxO and DAF-12/VDR act cell-autonomously to control specific cell type remodeling. Additionally, non-cell autonomous functions of DAF-16/FoxO and DAF-12/VDR in nervous system remodeling were uncovered, suggesting the presence of insulin-dependent interorgan signaling axes.
Article
Developmental Biology
Tessa Tekieli, Eviatar Yemini, Amin Nejatbakhsh, Chen Wang, Erdem Varol, Robert W. Fernandez, Neda Masoudi, Liam Paninski, Oliver Hobert
Summary: Researchers used a multicolor reporter transgene, NeuroPAL, to visualize the distinct identities of all male-specific neurons in the nematode Caenorhabditis elegans and conducted related studies. By analyzing the effects of removing developmental patterning genes on neuronal identity acquisition, researchers concluded that male-specific neurons execute their terminal differentiation program in a coordinated manner in the fourth larval stage.
Review
Neurosciences
Oliver Hobert
Summary: This article discusses the significance of Homeobox genes in specifying neuronal identity in animal nervous systems, emphasizing the method of defining neuron types through cell-type-specific gene battery expression.
NATURE REVIEWS NEUROSCIENCE
(2021)
Editorial Material
Genetics & Heredity
Adam J. Isabella, Eduardo Leyva-Diaz, Takuya Kaneko, Scott J. Gratz, Cecilia B. Moens, Oliver Hobert, Kate O'Connor-Giles, Rajan Thakur, Haosheng Sun
G3-GENES GENOMES GENETICS
(2021)
Editorial Material
Genetics & Heredity
Adam J. Isabella, Eduardo Leyva-Diaz, Takuya Kaneko, Scott J. Gratz, Cecilia B. Moens, Oliver Hobert, Kate O'Connor-Giles, Rajan Thakur, HaoSheng Sun
Article
Multidisciplinary Sciences
HaoSheng Sun, Oliver Hobert
Summary: This study using the model organism Caenorhabditis elegans reveals that post-mitotic nervous system undergoes distinct functional and molecular states across temporal transitions during post-embryonic development. The regulation of neuron-type-specific gene expression by the conserved miRNA LIN-4 and its target lin-14 plays a crucial role in promoting a mature neuronal transcriptional program. The findings provide insights into regulatory strategies controlling distinct behavioral states across temporal, sexual, and environmental dimensions during post-embryonic development.
Article
Biochemistry & Molecular Biology
Eduardo Leyva-Diaz, Oliver Hobert
Summary: The CUT family of homeobox genes control the specification of pan-neuronal identity in Caenorhabditis elegans. The effects on pan-neuronal gene expression and global nervous system function are minimal in single CUT mutants, but become more pronounced and worsen upon removal of additional CUT family members. Gene dosage is critical for the function of the CUT gene family.
Article
Biology
Berta Vidal, Burcu Gulez, Wen Xi Cao, Eduardo Leyva-Diaz, Molly B. Reilly, Tessa Tekieli, Oliver Hobert
Summary: This study describes the regulatory logic of the enteric nervous system differentiation in the nematode Caenorhabditis elegans, showing that the gene ceh-34 plays a critical role in the neuron type-specific terminal differentiation program. The cooperation between ceh-34 and different homeodomain transcription factors is also highlighted. These findings contribute to understanding neuronal identity specification and the control of neuronal circuit assembly in the enteric nervous system, and raise speculations about the early evolution of nervous systems.
Article
Biochemistry & Molecular Biology
Jingfang Yu, Merly C. Vogt, Bennett W. Fox, Chester J. J. Wrobel, Diana Fajardo Palomino, Brian J. Curtis, Bingsen Zhang, Henry H. Le, Arnaud Tauffenberger, Oliver Hobert, Frank C. Schroeder
Summary: Untargeted comparative metabolomics revealed the biosynthesis and metabolism pathways of serotonin in nonneuronal tissues, suggesting its important roles in serotonin-dependent phenotypes in C. elegans. Serotonin is abundantly produced in nonneuronal tissues via phenylalanine hydroxylase, in addition to its canonical biosynthesis in neurons via tryptophan hydroxylase. Most serotonin in C. elegans is incorporated into N-acetylserotonin-derived glucosides and further modified via the carboxylesterase CEST-4. Bacterial indole production interacts with serotonin metabolism via CEST-4. These findings indicate the significance of nonneuronal serotonin biosynthesis and metabolism in contributing to serotonin-dependent phenotypes.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Cyril Cros, Oliver Hobert
Summary: The classification of neurons reflects their similarity, and distinct subclasses can be formed through the regulation of key genes. This mechanism is observed in sensory and motor neurons in Caenorhabditis elegans.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Developmental Biology
Neda Masoudi, Ralf Schnabel, Eviatar Yemini, Eduardo Leyva-Diaz, Oliver Hobert
Summary: We investigated whether there are common mechanisms of neurogenesis throughout the entire nervous system of C. elegans. Our findings suggest that while distinct proneural class II bHLH factors play a role in neurogenesis, their function is not universal and is instead limited by lineage, cell type, and differentiation programs affected. Genetic removal of the hlh-2 gene activity showed broad effects on neurogenesis but still allowed for normal neurogenesis in many neuron-producing lineages.
Correction
Biochemistry & Molecular Biology
Jingfang Yu, Merly C. Vogt, Bennett W. Fox, Chester J. J. Wrobel, Diana Fajardo Palomino, Brian J. Curtis, Bingsen Zhang, Henry H. Le, Arnaud Tauffenberger, Oliver Hobert, Frank C. Schroeder
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Steven J. Cook, Cristine A. Kalinski, Oliver Hobert
Summary: The selection of synaptic connections can be explained by adjacency and cellular arrangement, supporting Peters' rule. By evaluating the connectome of C. elegans, it is found that synaptic specificity can be accurately modeled by neurite adjacency and brain strata, providing strong support for Peters' rule as an organizational principle of C. elegans brain wiring.
Article
Multidisciplinary Sciences
Merly C. Vogt, Oliver Hobert
Summary: Exposure to adverse nutritional and metabolic environments during critical periods of development can have lasting effects on individuals and their descendants. However, the specific signaling pathways and mechanisms responsible for these effects are still not well understood. Through experiments with Caenorhabditis elegans, researchers have discovered that changes in DAF-16/FoxO activity, a downstream target of insulin/IGF-1 receptor signaling, are responsible for metabolic programming phenotypes. The study also found that DAF-16/FoxO acts in somatic tissues, rather than directly in the germline, to initiate and manifest these programming effects.
