scholarly journals Aberrant Information Transfer Interferes with Functional Axon Regeneration

2018 ◽  
Author(s):  
Chen Ding ◽  
Marc Hammarlund
Keyword(s):  
Information Transfer ◽  
Single Neuron ◽  
Axon Regeneration ◽  
Behavioral Recovery ◽  
C Elegans ◽  
The Reformation ◽  
Functional Regeneration ◽  
Key Variables ◽  
And Function ◽  
Circuit Function

AbstractFunctional axon regeneration requires regenerating neurons to restore appropriate synaptic connectivity and circuit function. To model this process, we developed a single-neuron assay in C. elegans that links axon regeneration and synapse reformation with recovery of relevant behavior. After axon injury to the DA9 neuron, regeneration restores synapses to their pre-injury location. Surprisingly, presynapses also accumulate in the dendrite. Both axonal and dendritic synapses are functional. Dendritic synapses result in information misrouting that suppresses behavioral recovery. Formation of dendritic synapses is specifically dependent on dynein-mediated transport and jnk-1. However, even when information transfer is corrected, axonal synapses fail to adequately transmit information. Our study reveals unexpected plasticity during functional regeneration. Regeneration of the axon is not sufficient for the reformation of correct neuronal circuits after injury. Rather, synapse reformation and function are also key variables, and manipulation of circuit reformation improves behavioral recovery.

scholarly journals Aberrant information transfer interferes with functional axon regeneration

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Chen Ding ◽  
Marc Hammarlund
Keyword(s):  
Information Transfer ◽  
Synapse Formation ◽  
Axon Regeneration ◽  
Behavioral Recovery ◽  
Axon Injury ◽  
Functional Regeneration ◽  
Key Variables ◽  
And Function ◽  
Circuit Function ◽  
Molecular Components

Functional axon regeneration requires regenerating neurons to restore appropriate synaptic connectivity and circuit function. To model this process, we developed an assay in Caenorhabditis elegans that links axon and synapse regeneration of a single neuron to recovery of behavior. After axon injury and regeneration of the DA9 neuron, synapses reform at their pre-injury location. However, these regenerated synapses often lack key molecular components. Further, synaptic vesicles accumulate in the dendrite in response to axon injury. Dendritic vesicle release results in information misrouting that suppresses behavioral recovery. Dendritic synapse formation depends on dynein and jnk-1. But even when information transfer is corrected, axonal synapses fail to adequately transmit information. Our study reveals unexpected plasticity during functional regeneration. Regeneration of the axon is not sufficient for the reformation of correct neuronal circuits after injury. Rather, synapse reformation and function are also key variables, and manipulation of circuit reformation improves behavioral recovery.

scholarly journals The Amyloid Precursor-like Protein APL-1 Regulates Axon Regeneration

2018 ◽  
Author(s):  
Lewie Zeng ◽  
Rachid El Bejjani ◽  
Marc Hammarlund
Keyword(s):  
Motor Neurons ◽  
Neuronal Development ◽  
Axon Regeneration ◽  
Neuronal Response ◽  
Small Gtpase ◽  
C Elegans ◽  
Protein Levels ◽  
Mature Neurons ◽  
And Function

AbstractMembers of the Amyloid Precursor Protein (APP) family have important functions during neuronal development. However, their physiological functions in the mature nervous system are not fully understood. Here we use the C. elegans GABAergic motor neurons to study the post-developmental function of the APP-like protein APL-1 in vivo. We find that apl-1 has minimum roles in the maintenance of gross neuron morphology and function. However, we show that apl-1 is an inhibitor of axon regeneration, acting on mature neurons to limit regrowth in response to injury. The small GTPase Rab6/RAB-6.2 also inhibits regeneration, and does so in part by maintaining protein levels of APL-1. To inhibit regeneration, APL-1 functions via the E2 domain of its ectodomain; the cytoplasmic tail, transmembrane anchoring, and the E1 domain are not required for this function. Our data defines a novel role for APL-1 in modulating the neuronal response to injury.

Narrow is the Gate to Utopia

Moreana ◽  
2012 ◽  
Vol 49 (Number 187- (1-2) ◽  
pp. 207-226
Author(s):  
Marie-Claire Phélippeau
Keyword(s):  
Social Construction ◽  
Free Will ◽  
Religious Toleration ◽  
Individual Liberty ◽  
The Reformation ◽  
The Individual ◽  
And Function

This study examines the notions of pleasure, individual liberty and consensus in Thomas More’s Utopia. The paradox inherent in Utopia, written before the Reformation, is especially visible in the affirmation of religious toleration coexisting with the need for a strict supervision of the citizens. The dream of an ideal republic is based on a Pauline vision of man which defines the individual mainly as a sinner. Consequently, it is the duty of the republic’s rulers to guide the citizens and establish a consensus. This study tries to determine the part left to the individual’s free will and examines the nature and function of the structures that are supposed to ensure the happiness of each one and of the whole community. The notion of moral hierarchy is asserted as the linchpin of the Utopian social construction.

scholarly journals The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

scholarly journals C. elegans germ granules require both assembly and localized regulators for mRNA repression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Scott Takeo Aoki ◽  
Tina R. Lynch ◽  
Sarah L. Crittenden ◽  
Craig A. Bingman ◽  
Marvin Wickens ◽  
...  
Keyword(s):  
Liquid Droplet ◽  
Scaffolding Protein ◽  
P Granules ◽  
C Elegans ◽  
Cytoplasmic Rna ◽  
And Function ◽  
Rnp Granules ◽  
Key Residues ◽  
Reporter Mrna

AbstractCytoplasmic RNA–protein (RNP) granules have diverse biophysical properties, from liquid to solid, and play enigmatic roles in RNA metabolism. Nematode P granules are paradigmatic liquid droplet granules and central to germ cell development. Here we analyze a key P granule scaffolding protein, PGL-1, to investigate the functional relationship between P granule assembly and function. Using a protein–RNA tethering assay, we find that reporter mRNA expression is repressed when recruited to PGL-1. We determine the crystal structure of the PGL-1 N-terminal region to 1.5 Å, discover its dimerization, and identify key residues at the dimer interface. Mutations of those interface residues prevent P granule assembly in vivo, de-repress PGL-1 tethered mRNA, and reduce fertility. Therefore, PGL-1 dimerization lies at the heart of both P granule assembly and function. Finally, we identify the P granule-associated Argonaute WAGO-1 as crucial for repression of PGL-1 tethered mRNA. We conclude that P granule function requires both assembly and localized regulators.

hlh-12, a gene that is necessary and sufficient to promote migration of gonadal regulatory cells in C. elegans, evolved within the Caenorhabditis clade

Genetics ◽  
2021 ◽  
Author(s):  
Hana E Littleford ◽  
Karin Kiontke ◽  
David H A Fitch ◽  
Iva Greenwald
Keyword(s):  
Ectopic Expression ◽  
Morphological Diversity ◽  
Nematode Species ◽  
Bhlh Protein ◽  
Vulval Development ◽  
C Elegans ◽  
Form And Function ◽  
Somatic Gonad ◽  
And Function ◽  
Necessary And Sufficient

Abstract Specialized cells of the somatic gonad primordium of nematodes play important roles in the final form and function of the mature gonad. C. elegans hermaphrodites are somatic females that have a two-armed, U-shaped gonad that connects to the vulva at the midbody. The outgrowth of each gonad arm from the somatic gonad primordium is led by two female Distal Tip Cells (fDTC), while the Anchor Cell (AC) remains stationary and central to coordinate uterine and vulval development. The bHLH protein HLH-2 and its dimerization partners LIN-32 and HLH-12 had previously been shown to be required for fDTC specification. Here, we show that ectopic expression of both HLH-12 and LIN-32 in cells with AC potential transiently transforms them into fDTC-like cells. Furthermore, hlh-12 was known to be required for the fDTCs to sustain gonad arm outgrowth. Here, we show that ectopic expression of HLH-12 in the normally stationary AC causes displacement from its normal position, and that displacement likely results from activation of the leader program of fDTCs because it requires genes necessary for gonad arm outgrowth. Thus, HLH-12 is both necessary and sufficient to promote gonadal regulatory cell migration. As differences in female gonadal morphology of different nematode species reflect differences in the fate or migratory properties of the fDTCs or of the AC, we hypothesized that evolutionary changes in the expression of hlh-12 may underlie evolution of such morphological diversity. However, we were unable to identify an hlh-12 ortholog outside of Caenorhabditis. Instead, by performing a comprehensive phylogenetic analysis of all Class II bHLH proteins in multiple nematode species, we found that HLH-12 evolved within the Caenorhabditis clade, possibly by duplicative transposition of hlh-10. Our analysis suggests that control of gene regulatory hierarchies for gonadogenesis can be remarkably plastic during evolution without adverse phenotypic consequence.

scholarly journals The Genomic Distribution and Function of Histone Variant HTZ-1 during C. elegans Embryogenesis

PLoS Genetics ◽  
2008 ◽  
Vol 4 (9) ◽  
pp. e1000187 ◽  
Author(s):  
Christina M. Whittle ◽  
Karissa N. McClinic ◽  
Sevinc Ercan ◽  
Xinmin Zhang ◽  
Roland D. Green ◽  
...  
Keyword(s):  
Histone Variant ◽  
Genomic Distribution ◽  
C Elegans ◽  
And Function

scholarly journals Zebrafish Dscaml1 is Essential for Retinal Patterning and Function of Oculomotor Subcircuits

2019 ◽  
Author(s):  
Manxiu Ma ◽  
Alexandro D. Ramirez ◽  
Tong Wang ◽  
Rachel L. Roberts ◽  
Katherine E. Harmon ◽  
...  
Keyword(s):  
Animal Model ◽  
Light Adaptation ◽  
Neural Circuit ◽  
Oculomotor System ◽  
Gaze Stabilization ◽  
Ocular Disorders ◽  
Motor Apraxia ◽  
Premotor Pathways ◽  
And Function ◽  
Circuit Function

AbstractDown Syndrome Cell Adhesion Molecules (dscam and dscaml1) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the role of dscaml1 in the zebrafish oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Loss of zebrafish dscaml1 resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses showed that mutants have abnormal gaze stabilization, impaired fixation, disconjugation, and faster fatigue. Notably, the saccade and fatigue phenotypes in dscaml1 mutants are reminiscent of human ocular motor apraxia, for which no animal model exists. Two-photon calcium imaging showed that loss of dscaml1 leads to impairment in the saccadic premotor pathway but not the pretectum-vestibular premotor pathway, indicating a subcircuit requirement for dscaml1. Together, we show that dscaml1 has both broad and specific roles in oculomotor circuit function, providing a new animal model to investigate the development of premotor pathways and their associated human ocular disorders.

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