scholarly journals Repression of an activity-dependent autocrine insulin signal is required for sensory neuron development in C. elegans

Development ◽  
2019 ◽  
Vol 146 (22) ◽  
pp. dev182873 ◽  
Author(s):  
Lauren Bayer Horowitz ◽  
Julia P. Brandt ◽  
Niels Ringstad
Keyword(s):  
Sensory Neuron ◽  
Neuron Development ◽  
Insulin Signal ◽  
C Elegans ◽  
Activity Dependent

scholarly journals Long-term activity drives dendritic branch elaboration of a C. elegans sensory neuron

2019 ◽  
Author(s):  
Jesse A Cohn ◽  
Elizabeth R Cebul ◽  
Giulio Valperga ◽  
Mario de Bono ◽  
Maxwell G Heiman ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Neuronal Activity ◽  
Morphological Changes ◽  
Model Organism ◽  
Neuronal Morphology ◽  
Sensory Transduction ◽  
Central Component ◽  
C Elegans ◽  
Activity Dependent

ABSTRACTNeuronal activity often leads to alterations in gene expression and cellular architecture. The nematode Caenorhabditis elegans, owing to its compact translucent nervous system, is a powerful system in which to study conserved aspects of the development and plasticity of neuronal morphology. Here we focus on one sensory neuron in the worm, termed URX, which senses oxygen and signals tonically proportional to environmental oxygen. Previous studies have reported that URX has variable branched endings at its dendritic sensory tip. By controlling oxygen levels and analyzing mutants, we found that these branched endings grow over time as a consequence of neuronal activity. Furthermore, we observed that the branches contain microtubules, but do not appear to harbor the guanylyl cyclase GCY-35, a central component of the oxygen sensory transduction pathway. Interestingly, we found that although URX dendritic tips grow branches in response to long-term activity, the degree of branch elaboration does not correlate with oxygen sensitivity at the cellular or the behavioral level. Given the strengths of C. elegans as a model organism, URX may serve as a potent system for uncovering genes and mechanisms involved in activity-dependent morphological changes in neurons.

scholarly journals Repression of an activity-dependent autocrine insulin signal is required for sensory neuron development in C. elegans

2018 ◽  
Author(s):  
Lauren Bayer Horowitz ◽  
Julia P. Brandt ◽  
Niels Ringstad
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
P38 Map Kinase ◽  
Dependent Manner ◽  
Neuron Development ◽  
C Elegans ◽  
Chemosensory Neuron ◽  
Insulin Receptor Signaling ◽  
Activity Dependent

AbstractNervous system development is instructed both by genetic programs and activity-dependent refinement of gene expression and connectivity. How these mechanisms are integrated remains poorly understood. Here, we report that the regulated release of insulin-like peptides (ILPs) during development of the C. elegans nervous system accomplishes such an integration. We find that the p38 MAP kinase PMK-3, which is required for the differentiation of chemosensory BAG neurons, functions by limiting expression of an autocrine ILP signal that represses a chemosensory-neuron fate. ILPs are released from BAGs in an activity-dependent manner during embryonic development, and regulate neurodifferentiation through a non-canonical insulin receptor signaling pathway. The differentiation of a specialized neuron-type is, therefore, coordinately regulated by a genetic program that controls ILP expression and by neural activity, which regulates ILP release. Autocrine signals of this kind may have general and conserved functions as integrators of deterministic genetic programs with activity-dependent mechanisms during neurodevelopment.

scholarly journals Girdin regulates dendrite morphogenesis and cilium position in two specialized sensory neuron types in C. elegans

2020 ◽  
Author(s):  
Inna Nechipurenko ◽  
Sofia Lavrentyeva ◽  
Piali Sengupta
Keyword(s):  
Sensory Neuron ◽  
Primary Cilia ◽  
Gas Sensing ◽  
Neuron Development ◽  
Dendrite Morphology ◽  
Sensory Stimuli ◽  
Multifunctional Protein ◽  
C Elegans ◽  
Dendrite Development ◽  
Dendrite Morphogenesis

ABSTRACTPrimary cilia are located at the dendritic tips of sensory neurons and house the molecular machinery necessary for detection and transduction of sensory stimuli. The mechanisms that coordinate dendrite extension with cilium position during sensory neuron development are not well understood. Here, we show that GRDN-1, the Caenorhabditis elegans ortholog of the highly conserved scaffold and signaling protein Girdin/GIV, regulates both cilium position and dendrite extension in the postembryonic AQR and PQR gas-sensing neurons. Mutations in grdn-1 disrupt dendrite outgrowth and mislocalize cilia to the soma or proximal axonal segments in AQR, and to a lesser extent, in PQR. GRDN-1 is localized to the basal body and regulates localization of HMR-1/Cadherin to the distal AQR dendrite. However, loss of HMR-1 and/or SAX-7/LICAM, molecules previously implicated in sensory dendrite development in C. elegans, do not alter AQR dendrite morphology or cilium position. We demonstrate that GRDN-1 localization in AQR is regulated by UNC-116/Kinesin-1, and that correspondingly, unc-116 mutants exhibit severe AQR dendrite outgrowth and cilium positioning defects. In contrast, GRDN-1 and cilium localization in PQR is modulated by LIN-44/Wnt signaling. Together, these findings identify upstream regulators of GRDN-1, and describe new cellspecific roles for this multifunctional protein in sensory dendrite development.

scholarly journals Accelerating Gene Discovery by Phenotyping Whole-Genome Sequenced Multi-Mutation Strains and Using the Sequence Kernel Association Test (SKAT)

2015 ◽  
Author(s):  
Tiffany A. Timbers ◽  
Stephanie J. Garland ◽  
Swetha Mohan ◽  
Stephane Flibotte ◽  
Mark Edgley ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Biological Process ◽  
Gene Discovery ◽  
Whole Genome ◽  
Sequence Kernel Association Test ◽  
Reverse Genetic ◽  
Neuron Development ◽  
Genetic Screens ◽  
C Elegans

AbstractForward genetic screens represent powerful, unbiased approaches to uncover novel components in any biological process. Such screens suffer from a major bottleneck, however, namely the cloning of corresponding genes causing the phenotypic variation. Reverse genetic screens have been employed as a way to circumvent this issue, but can often be limited in scope. Here we demonstrate an innovative approach to gene discovery. Using C. elegans as a model system, we used a whole-genome sequenced multi-mutation library, from the Million Mutation Project, together with the Sequence Kernel Association Test (SKAT), to rapidly screen for and identify genes associated with a phenotype of interest, namely defects in dye-filling of ciliated sensory neurons. Such anomalies in dye-filling are often associated with the disruption of cilia, organelles which in humans are implicated in sensory physiology (including vision, smell and hearing), development and disease. Beyond identifying several well characterised dye-filling genes, our approach uncovered three genes not previously linked to ciliated sensory neuron development or function. From these putative novel dye-filling genes, we confirmed the involvement of BGNT–1.1 in ciliated sensory neuron function and morphogenesis. BGNT–1.1 functions at the trans-Golgi network of sheath cells (glia) to influence dye-filling and cilium length, in a cell non-autonomous manner. Notably, BGNT–1.1 is the orthologue of human B3GNT1/B4GAT1, a glycosyltransferase associated with Walker-Warburg syndrome (WWS). WWS is a multigenic disorder characterised by muscular dystrophy as well as brain and eye anomalies. Together, our work unveils an effective and innovative approach to gene discovery, and provides the first evidence that B3GNT1-associated Walker-Warburg syndrome may be considered a ciliopathy.Author SummaryModel organisms are useful tools for uncovering new genes involved in a biological process via genetic screens. Such an approach is powerful, but suffers from drawbacks that can slow down gene discovery. In forward genetics screens, difficult-to-map phenotypes present daunting challenges, and whole-genome coverage can be equally challenging for reverse genetic screens where typically only a single gene’s function is assayed per strain. Here, we show a different approach which includes positive aspects of forward (high-coverage, randomly-induced mutations) and reverse genetics (prior knowledge of gene disruption) to accelerate gene discovery. We paired a whole-genome sequenced multi-mutation C. elegans library with a rare-variant associated test to rapidly identify genes associated with a phenotype of interest: defects in sensory neurons bearing sensory organelles called cilia, via a simple dye-filling assay to probe the form and function of these cells. We found two well characterised dye-filling genes and three genes, not previously linked to ciliated sensory neuron development or function, that were associated with dye-filling defects. We reveal that disruption of one of these (BGNT–1.1), whose human orthologue is associated with Walker-Warburg syndrome, results in abrogated uptake of dye and cilia length defects. We believe that our novel approach is useful for any organism with a small genome that can be quickly sequenced and where many mutant strains can be easily isolated and phenotyped, such as Drosophila and Arabidopsis.

scholarly journals Frizzled-10 promotes sensory neuron development in Xenopus embryos

2009 ◽  
Vol 335 (1) ◽  
pp. 143-155 ◽  
Author(s):  
Carla Garcia-Morales ◽  
Chiung-Hui Liu ◽  
Muhammad Abu-Elmagd ◽  
Mohammad K. Hajihosseini ◽  
Grant N. Wheeler
Keyword(s):  
Sensory Neuron ◽  
Neuron Development ◽  
Xenopus Embryos

scholarly journals Development and validation of an in vitro model system to study peripheral sensory neuron development and injury

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Iwan Jones ◽  
Tushar Devanand Yelhekar ◽  
Rebecca Wiberg ◽  
Paul J. Kingham ◽  
Staffan Johansson ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
In Vitro Model ◽  
Model System ◽  
Neuron Development ◽  
In Vitro Model System ◽  
Vitro Model ◽  
Development And Validation ◽  
Peripheral Sensory
Sign in / Sign up

Export Citation Format

Share Document