C. elegans REMO-1, a glial GPCR, regulates stress-induced nervous system remodeling and behavior

Animal nervous systems remodel following stress. Although global stress-dependent changes are well documented, contributions of individual neuron remodeling events to animal behavior modification are challenging to study. In response to environmental insults, C. elegans become stress-resistant dauers. Dauer entry induces amphid sensory-organ remodeling, in which bilateral AMsh glial cells expand and fuse, allowing embedded AWC chemosensory neurons to extend sensory receptive endings. We show that amphid remodeling accelerates dauer exit upon exposure to favorable conditions, and identify a G protein-coupled receptor, REMO-1, driving AMsh glia fusion, AWC neuron remodeling, and dauer exit. REMO-1 is expressed in and localizes to AMsh glia tips, is dispensable for other remodeling events, and promotes stress-induced expression of the remodeling receptor tyrosine kinase VER-1. Our results demonstrate how single-neuron structural changes affect animal behavior, identify key glial roles in stress-induced nervous system shape changes, and demonstrate that remodeling primes animals to respond to favorable conditions.

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Neuronal GPCR NPR-8 regulates C. elegans defense against pathogen infection

Science Advances ◽

10.1126/sciadv.aaw4717 ◽

2019 ◽

Vol 5 (11) ◽

pp. eaaw4717 ◽

Cited By ~ 2

Author(s):

Durai Sellegounder ◽

Yiyong Liu ◽

Phillip Wibisono ◽

Chia-Hui Chen ◽

David Leap ◽

...

Keyword(s):

Nervous System ◽

Sensory Neurons ◽

Host Defenses ◽

Physical Barrier ◽

Pathogen Infection ◽

Innate Defense ◽

C Elegans ◽

Collagen Expression ◽

Collagen Genes ◽

G Protein Coupled

Increasing evidence indicates that infection-triggered host defenses are regulated by the nervous system. However, the precise mechanisms of this regulation are not well understood. Here, we demonstrate that neuronal G protein-coupled receptor NPR-8 negatively regulates Caenorhabditis elegans defense against pathogen infection by suppressing cuticular collagen expression. NPR-8 controls the dynamics of cuticle structure in response to infection, likely through its regulation of cuticular collagen genes which, in turn, affects the nematode’s defense. We further show that the defense activity of NPR-8 is confined to amphid sensory neurons AWB, ASJ, and AWC. It is generally believed that physical barrier defenses are not a response to infections but are part of the body’s basic innate defense against pathogens. Our results challenge this view by showing not only that C. elegans cuticle structure dynamically changes in response to infection but also that the cuticle barrier defense is regulated by the nervous system.

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The Small, Secreted Immunoglobulin Protein ZIG-3 Maintains Axon Position in Caenorhabditis elegans

Genetics ◽

10.1534/genetics.109.107441 ◽

2009 ◽

Vol 183 (3) ◽

pp. 917-927 ◽

Cited By ~ 18

Author(s):

Claire Bénard ◽

Nartono Tjoe ◽

Thomas Boulin ◽

Janine Recio ◽

Oliver Hobert

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Single Neuron ◽

Tissue Type ◽

Mechanical Forces ◽

C Elegans ◽

Link Type ◽

Maintenance Factors ◽

L1 Protein ◽

Ig Domain

Vertebrate and invertebrate genomes contain scores of small secreted or transmembrane proteins with two immunoglobulin (Ig) domains. Many of them are expressed in the nervous system, yet their function is not well understood. We analyze here knockout alleles of all eight members of a family of small secreted or transmembrane Ig domain proteins, encoded by the Caenorhabditis elegans zig (“zwei Ig Domänen”) genes. Most of these family members display the unusual feature of being coexpressed in a single neuron, PVT, whose axon is located along the ventral midline of C. elegans. One of these genes, zig-4, has previously been found to be required for maintaining axon position postembryonically in the ventral nerve cord of C. elegans. We show here that loss of zig-3 function results in similar postdevelopmental axon maintenance defects. The maintenance function of both zig-3 and zig-4 serves to counteract mechanical forces that push axons around, as well as various intrinsic attractive forces between axons that cause axon displacement if zig genes like zig-3 or zig-4 are deleted. Even though zig-3 is expressed only in a limited number of neurons, including PVT, transgenic rescue experiments show that zig-3 can function irrespective of which cell or tissue type it is expressed in. Double mutant analysis shows that zig-3 and zig-4 act together to affect axon maintenance, yet they are not functionally interchangeable. Both genes also act together with other, previously described axon maintenance factors, such as the Ig domain proteins DIG-1 and SAX-7, the C. elegans ortholog of the human L1 protein. Our studies shed further light on the use of dedicated factors to maintain nervous system architecture and corroborate the complexity of the mechanisms involved.

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Caenorhabditis elegans Olfaction

Oxford Research Encyclopedia of Neuroscience ◽

10.1093/acrefore/9780190264086.013.191 ◽

2017 ◽

Author(s):

Douglas K. Reilly ◽

Jagan Srinivasan

Keyword(s):

Nervous System ◽

Caenorhabditis Elegans ◽

Environmental Chemical ◽

Olfactory Neurons ◽

C Elegans ◽

Chemical Structures ◽

Olfactory Sensation ◽

Abiotic Stimuli ◽

And Behavior ◽

Crowded Environments

To survive, animals must properly sense their surrounding environment. The types of sensation that allow for detecting these changes can be categorized as tactile, thermal, aural, or olfactory. Olfaction is one of the most primitive senses, involving the detection of environmental chemical cues. Organisms must sense and discriminate between abiotic and biogenic cues, necessitating a system that can react and respond to changes quickly. The nematode, Caenorhabditis elegans, offers a unique set of tools for studying the biology of olfactory sensation. The olfactory system in C. elegans is comprised of 14 pairs of amphid neurons in the head and two pairs of phasmid neurons in the tail. The male nervous system contains an additional 89 neurons, many of which are exposed to the environment and contribute to olfaction. The cues sensed by these olfactory neurons initiate a multitude of responses, ranging from developmental changes to behavioral responses. Environmental cues might initiate entry into or exit from a long-lived alternative larval developmental stage (dauer), or pheromonal stimuli may attract sexually mature mates, or repel conspecifics in crowded environments. C. elegans are also capable of sensing abiotic stimuli, exhibiting attraction and repulsion to diverse classes of chemicals. Unlike canonical mammalian olfactory neurons, C. elegans chemosensory neurons express more than one receptor per cell. This enables detection of hundreds of chemical structures and concentrations by a chemosensory nervous system with few cells. However, each neuron detects certain classes of olfactory cues, and, combined with their synaptic pathways, elicit similar responses (i.e., aversive behaviors). The functional architecture of this chemosensory system is capable of supporting the development and behavior of nematodes in a manner efficient enough to allow for the genus to have a cosmopolitan distribution.

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Changes in postural syntax characterize sensory modulation and natural variation of C. elegans locomotion

10.1101/017707 ◽

2015 ◽

Author(s):

Roland F. Schwarz ◽

Robyn Branicky ◽

Laura J. Grundy ◽

William R. Schafer ◽

André E.X. Brown

Keyword(s):

Nervous System ◽

Language Processing ◽

Natural Variation ◽

Sensory Modulation ◽

Comprehensive Understanding ◽

C Elegans ◽

Locomotor Behaviour ◽

Discrete Representation ◽

Heavy Tailed ◽

Shape Changes

Locomotion is driven by shape changes coordinated by the nervous system through time; thus, enumerating an animal's complete repertoire of shape transitions would provide a basis for a comprehensive understanding of locomotor behaviour. Here we introduce a discrete representation of behaviour in the nematode C. elegans. At each point in time, the worm's posture is approximated by its closest matching template from a set of 90 postures and locomotion is represented as sequences of postures. The frequency distribution of postural sequences is heavy-tailed with a core of frequent behaviours and a much larger set of rarely used behaviours. Responses to optogenetic and environmental stimuli can be quantified as changes in postural syntax: worms show different preferences for different sequences of postures drawn from the same set of templates. A discrete representation of behaviour will enable the use of methods developed for other kinds of discrete data in bioinformatics and language processing to be harnessed for the study of behaviour.

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Glia actively sculpt sensory neurons by controlled phagocytosis to tune animal behavior

10.1101/2020.11.11.378893 ◽

2020 ◽

Author(s):

Stephan Raiders ◽

Erik Calvin Black ◽

Andrea Bae ◽

Stephen MacFarlane ◽

Shai Shaham ◽

...

Keyword(s):

Animal Behavior ◽

Sensory Input ◽

Single Neuron ◽

Sense Organ ◽

Photoreceptor Outer Segments ◽

C Elegans ◽

Rac1 Gtpase ◽

The Central Nervous System ◽

Membrane Sealing ◽

Sensory Endings

ABSTRACTGlia in the central nervous system engulf neuron fragments during synapse remodeling and recycling of photoreceptor outer-segments. Whether glia passively clear shed neuronal debris, or actively remove neuron fragments is unknown. How pruning of single-neuron endings impacts animal behavior is also unclear. Here we report that adult C. elegans AMsh glia engulf sensory endings of the AFD thermosensory neuron. Engulfment is regulated by temperature, AFD’s sensory input, and tracks AFD activity. Phosphatidylserine (PS) flippase TAT-1/ATP8A, functions with glial PS-receptor PSR-1/PSR and PAT-2/α-integrin to initiate engulfment. Glial CED-10/Rac1 GTPase, acting through a conserved GEF complex, executes phagocytosis using the actin-remodeler WSP-1/nWASp and the membrane-sealing factor EFF-1 fusogen. CED-10 levels determine engulfment rates, and engulfment-defective mutants exhibit altered AFD-ending shape and thermosensory behavior. Our findings reveal a molecular pathway underpinning glia-dependent phagocytosis in a peripheral sense-organ, and demonstrate that glia actively engulf neuron-fragments, with profound consequences on neuron shape and animal behavior.

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Transcriptional Control Of Calmodulin By CAMTA Regulates Neural Excitability

10.1101/2020.09.14.296137 ◽

2020 ◽

Author(s):

Thanh T. K. Vuong-Brender ◽

Sean M. Flynn ◽

Mario de Bono

Keyword(s):

Nervous System ◽

Transcriptional Control ◽

Neuronal Excitability ◽

Rna Seq ◽

Transcription Activator ◽

Neural Excitability ◽

C Elegans ◽

Chromatin Immunoprecipitation Sequencing ◽

Mutant Phenotypes ◽

And Behavior

AbstractCalmodulin (CaM) is the major calcium ion (Ca2+) sensor in many biological processes, regulating for example the CaM kinases, calcineurin, and many ion channels. CaM levels are limiting in cells compared to its myriad targets, but how CaM levels are controlled is poorly understood. We find that CaM abundance in the C. elegans and Drosophila nervous systems is controlled by the CaM-binding transcription activator, CAMTA. C. elegans CAMTA (CAMT-1), like its fly and mammalian orthologues, is expressed widely in the nervous system. camt-1 mutants display pleiotropic behavioural defects and altered Ca2+ signaling in neurons. Using FACS-RNA Seq we profile multiple neural types in camt-1 mutants and find all exhibit reduced CaM mRNA compared to controls. Supplementing CaM levels using a transgene rescues camt-1 mutant phenotypes. Chromatin immunoprecipitation sequencing (ChIP-Seq) data show that CAMT-1 binds several sites in the calmodulin promoter. CRISPR-mediated deletion of these sites shows they redundantly regulate calmodulin expression. We also find that CaM can feed back to inhibit its own expression by a mechanism that depends on CaM binding sites on CAMT-1. This work uncovers a mechanism that can both activate and inhibit CaM expression in the nervous system, and controls Ca2+ homeostasis, neuronal excitability and behavior.

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Glia actively sculpt sensory neurons by controlled phagocytosis to tune animal behavior

eLife ◽

10.7554/elife.63532 ◽

2021 ◽

Vol 10 ◽

Author(s):

Stephan Raiders ◽

Erik Calvin Black ◽

Andrea Bae ◽

Stephen MacFarlane ◽

Mason Klein ◽

...

Keyword(s):

Animal Behavior ◽

Sensory Input ◽

Single Neuron ◽

Sense Organ ◽

Neuron Activity ◽

Photoreceptor Outer Segments ◽

C Elegans ◽

Rac1 Gtpase ◽

The Central Nervous System ◽

Sensory Endings

Glia in the central nervous system engulf neuron fragments to remodel synapses and recycle photoreceptor outer-segments. Whether glia passively clear shed neuronal debris, or actively prune neuron fragments is unknown. How pruning of single-neuron endings impacts animal behavior is also unclear. Here we report our discovery of glia-directed neuron pruning in C. elegans. Adult C. elegans AMsh glia engulf sensory endings of the AFD thermosensory neuron by repurposing components of the conserved apoptotic corpse phagocytosis machinery. The phosphatidylserine (PS) flippase TAT-1/ATP8A, functions with glial PS-receptor PSR-1/PSR and PAT-2/α-integrin to initiate engulfment. This activates glial CED-10/Rac1 GTPase through the ternary GEF complex of CED-2/CrkII, CED-5/DOCK180, CED-12/ELMO. Execution of phagocytosis uses the actin-remodeler WSP-1/nWASp. This process dynamically tracks AFD activity and is regulated by temperature, the AFD sensory input. Importantly, glial CED-10 levels regulate engulfment rates downstream of neuron activity, and engulfment-defective mutants exhibit altered AFD-ending shape and thermosensory behavior. Our findings reveal a molecular pathway underlying glia-dependent engulfment in a peripheral sense-organ, and demonstrate that glia actively engulf neuron-fragments, with profound consequences on neuron shape and animal sensory behavior.

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