ENS - Départment de biologie

Natural Viruses of Caenorhabditis Nematodes.

Frédérique Godfroid — 2020-01-17T07:44:13Z

Abstract

Caenorhabditis elegans has long been a laboratory model organism with no known natural pathogens. In the past ten years, however, natural viruses have been isolated from wild-caught C. elegans (Orsay virus) and its relative Caenorhabditis briggsae (Santeuil virus, Le Blanc virus, and Melnik virus). All are RNA positive-sense viruses related to Nodaviridae ; they infect intestinal cells and are horizontally transmitted. The Orsay virus capsid structure has been determined and the virus can be reconstituted by transgenesis of the host. Recent use of the Orsay virus has enabled researchers to identify evolutionarily conserved proviral and antiviral genes that function in nematodes and mammals. These pathways include endocytosis through SID-3 and WASP ; a uridylyltransferase that destabilizes viral RNAs by uridylation of their 3' end ; ubiquitin protein modifications and turnover ; and the RNA interference pathway, which recognizes and degrades viral RNA.

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Annu Rev Genet. 2019 Dec 3 ;53:313-326. doi : 10.1146/annurev-genet-112618-043756.

Vertical transmission in Caenorhabditis nematodes of RNA molecules encoding a viral RNA-dependent RNA polymerase.

Frédérique Godfroid — 2020-01-16T13:20:00Z

Abstract

Here, we report on the discovery in Caenorhabditis nematodes of multiple vertically transmitted RNAs coding for putative RNA-dependent RNA polymerases. Their sequences share similarity to distinct RNA viruses, including bunyaviruses, narnaviruses, and sobemoviruses. The sequences are present exclusively as RNA and are not found in DNA form. The RNAs persist in progeny after bleach treatment of adult animals, indicating vertical transmission of the RNAs. We tested one of the infected strains for transmission to an uninfected strain and found that mating of infected animals with uninfected animals resulted in infected progeny. By in situ hybridization, we detected several of these RNAs in the cytoplasm of the male and female germline of the nematode host. The Caenorhabditis hosts were found defective in degrading exogenous double-stranded RNAs, which may explain retention of viral-like RNAs. Strikingly, one strain, QG551, harbored three distinct virus-like RNA elements. Specific patterns of small RNAs complementary to the different viral-like RNAs were observed, suggesting that the different RNAs are differentially recognized by the RNA interference (RNAi) machinery. While vertical transmission of viruses in the family Narnaviridae, which are known as capsidless viruses, has been described in fungi, these observations provide evidence that multicellular animal cells harbor similar viruses.

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Proc Natl Acad Sci U S A. 2019 Dec 3 ;116(49):24738-24747. doi : 10.1073/pnas.1903903116.

Activity-dependent death of transient Cajal-Retzius neurons is required for functional cortical wiring

Frédérique Godfroid — 2020-01-14T17:11:30Z

Abstract

Programmed cell death and early activity contribute to the emergence of functional cortical circuits. While most neuronal populations are scaled-down by death, some subpopulations are entirely eliminated, raising the question of the importance of such demise for cortical wiring. Here, we addressed this issue by focusing on Cajal-Retzius neurons (CRs), key players in cortical development that are eliminated in postnatal mice in part via Bax-dependent apoptosis. Using Bax-conditional mutants and CR hyperpolarization, we show that the survival of electrically active subsets of CRs triggers an increase in both dendrite complexity and spine density of upper layer pyramidal neurons, leading to an excitation/inhibition imbalance. The survival of these CRs is induced by hyperpolarization, highlighting an interplay between early activity and neuronal elimination. Taken together, our study reveals a novel activity-dependent programmed cell death process required for the removal of transient immature neurons and the proper wiring of functional cortical circuits.

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Elife. 2019 Dec 31 ;8. pii : e50503. doi : 10.7554/eLife.50503.

Massive centriole production can occur in the absence of deuterosomes in multiciliated cells

Frédérique Godfroid — 2020-01-13T14:58:55Z

Abstract

Multiciliated cells (MCCs) amplify large numbers of centrioles that convert into basal bodies, which are required for producing multiple motile cilia. Most centrioles amplified by MCCs grow on the surface of organelles called deuterosomes, whereas a smaller number grow through the centriolar pathway in association with the two parent centrioles. Here, we show that MCCs lacking deuterosomes amplify the correct number of centrioles with normal step-wise kinetics. This is achieved through a massive production of centrioles on the surface and in the vicinity of parent centrioles. Therefore, deuterosomes may have evolved to relieve, rather than supplement, the centriolar pathway during multiciliogenesis. Remarkably, MCCs lacking parent centrioles and deuterosomes also amplify the appropriate number of centrioles inside a cloud of pericentriolar and fibrogranular material. These data show that the centriole number is set independently of their nucleation platforms and suggest that massive centriole production in MCCs is a robust process that can self-organize.

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Nat Cell Biol. 2019 Dec ;21(12):1544-1552. doi : 10.1038/s41556-019-0427-x.

Ultrafast Two-Photon Imaging of a High-Gain Voltage Indicator in Awake Behaving Mice.

Frédérique Godfroid — 2020-01-13T09:30:54Z

Authors

Vincent Villette, Mariya Chavarha, Ivan K.Dimov, Jonathan Bradley, Lagnajeet Pradhan, Benjamin Mathieu, Stephen W. Evans, Simon Chamberland, Dongqing Shi, Renzhi Yang, Benjamin B. Kim, Annick Ayon, Abdelali Jalil, François St-Pierre, Mark J.Schnitzer, GuoqiangBi, KatalinToth, Jun Ding, Michael Z. Lin

In Brief

The genetically encoded voltage indicator, ASAP3, provides improved voltage responses and activation kinetics that enable single-trial tracking of action potentials and subthreshold events with subcellular resolution deep in the mouse brain during behavioral tasks when imaged with ULoVE, a kilohertz-rate twophoton sampling method with increased stability and sensitivity.

Abstract

Optical interrogation of voltage in deep brain locations with cellular resolution would be immensely useful for understanding how neuronal circuits process information. Here, we report ASAP3, a genetically encoded voltage indicator with 51% fluorescence modulation by physiological voltages, submillisecond activation kinetics, and full responsivity under two-photon excitation. We also introduce an ultrafast local volume excitation (ULoVE) method for kilohertz-rate two-photon sampling in vivo with increased stability and sensitivity. Combining a soma-targeted ASAP3 variant and ULoVE, we show single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution and with repeated sampling over days. In the visual cortex, we use soma-targeted ASAP3 to illustrate cell-type-dependent subthreshold modulation by locomotion. Thus, ASAP3 and ULoVE enable high-speed optical recording of electrical activity in genetically defined neurons at deep locations during awake behavior.

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Cell. 2019 Dec 12 ;179(7):1590-1608.e23. doi : 10.1016/j.cell.2019.11.004.

Relaxed purifying selection in autopolyploids drives transposable element over-accumulation which provides variants for local adaptation

Frédérique Godfroid — 2020-01-07T13:32:48Z

Abstract

Polyploidization is frequently associated with increased transposable element (TE) content. However, what drives TE dynamics following whole genome duplication (WGD) and the evolutionary implications remain unclear. Here, we leverage whole-genome resequencing data available for 300 individuals of Arabidopsis arenosa, a well characterized natural diploid-autotetraploid plant species, to address these questions. Based on 43,176 TE insertions we detect in these genomes, we demonstrate that relaxed purifying selection rather than transposition bursts is the main driver of TE over-accumulation after WGD. Furthermore, the increased pool of TE insertions in tetraploids is especially enriched within or near environmentally responsive genes. Notably, we show that the major flowering-time repressor gene FLC is disrupted by a TE insertion specifically in the rapid-cycling tetraploid lineage that colonized mainland railways. Together, our findings indicate that tetrasomy leads to an enhanced accumulation of genic TE insertions, some of which likely contribute to local adaptation.

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Nat Commun. 2019 Dec 20 ;10(1):5818. doi : 10.1038/s41467-019-13730-0.

Cécile Charrier, lauréate de l'appel d'offre EMBO "Young Investigator" 2019.

Frédérique Godfroid — 2019-12-04T08:59:53Z

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Global Trends in Marine Plankton Diversity across Kingdoms of Life

Frédérique Godfroid — 2019-11-14T17:24:40Z

In Brief

The drivers of ocean plankton diversity across archaea, bacteria, eukaryotes, and major virus clades are inferred from both molecular and imaging data acquired by the Tara Oceans project and used to predict the effects of severe warming of the surface ocean on this critical ecosystem by the end of the 21st century.

Highlights

• Most epipelagic planktonic groups exhibit a poleward decline of diversity
• No latitudinal diversity gradient was observed below the photic zone
• Temperature emerges as the best predictor of epipelagic plankton diversity
• Global warming may increase plankton diversity, particularly at high latitudes

Summary

The ocean is home to myriad small planktonic organisms that underpin the functioning of marine ecosystems. However, their spatial patterns of diversity and the underlying drivers remain poorly known, precluding projections of their responses to global changes. Here we investigate the latitudinal gradients and global predictors of plankton diversity across archaea, bacteria, eukaryotes, and major virus clades using both molecular and imaging data from Tara Oceans. We show a decline of diversity for most planktonic groups toward the poles, mainly Q9 driven by decreasing ocean temperatures. Projections into the future suggest that severe warming of the surface ocean by the end of the 21st century could lead to tropicalization of the diversity of most planktonic groups in temperate and polar regions.
These changes may have multiple consequences for marine ecosystem functioning and services and are expected to be particularly significant in key areas for carbon sequestration, fisheries, and marine conservation.

Trans-synaptic signaling through the glutamate receptor delta-1 mediates inhibitory synapse formation in cortical pyramidal neurons

Frédérique Godfroid — 2019-11-13T15:01:41Z

Abstract
Fine orchestration of excitatory and inhibitory synaptic development is required for normal brain function, and alterations may cause neurodevelopmental disorders. Using sparse molecular manipulations in intact brain circuits, we show that the glutamate receptor delta-1 (GluD1), a member of ionotropic glutamate receptors (iGluRs), is a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. GluD1 is selectively required for the formation of inhibitory synapses and regulates GABAergic synaptic transmission accordingly. At inhibitory synapses, GluD1 interacts with cerebellin-4, an extracellular scaffolding protein secreted by somatostatin-expressing interneurons, which bridges postsynaptic GluD1 and presynaptic neurexins. When binding to its agonist glycine or D-serine, GluD1 elicits non-ionotropic postsynaptic signaling involving the guanine nucleotide exchange factor ARHGEF12 and the regulatory subunit of protein phosphatase 1 PPP1R12A. Thus, GluD1 defines a trans-synaptic interaction regulating postsynaptic signaling pathways for the proper establishment of cortical inhibitory connectivity and challenges the dichotomy between iGluRs and inhibitory synaptic molecules.

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Neuron. 2019 Oct 9. pii : S0896-6273(19)30801-3. doi : 10.1016/j.neuron.2019.09.027.

Sensorimotor Transformations in the Zebrafish Auditory System

Frédérique Godfroid — 2019-11-12T16:56:04Z

Abstract

Organisms use their sensory systems to acquire information from their environment and integrate this information to produce relevant behaviors. Nevertheless, how sensory information is converted into adequate motor patterns in the brain remains an open question. Here, we addressed this question using two-photon and light-sheet calcium imaging in intact, behaving zebrafish larvae. We monitored neural activity elicited by auditory stimuli while simultaneously recording tail movements. We observed a spatial organization of neural activity according to four different response profiles (frequency tuning curves), suggesting a low-dimensional representation of frequency information, maintained throughout the development of the larvae. Low frequencies (150-450 Hz) were locally processed in the hindbrain and elicited motor behaviors. In contrast, higher frequencies (900-1,000 Hz) rarely induced motor behaviors and were also represented in the midbrain. Finally, we found that the sensorimotor transformations in the zebrafish auditory system are a continuous and gradual process that involves the temporal integration of the sensory response in order to generate a motor behavior.

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Curr Biol. 2019 Nov 4. pii : S0960-9822(19)31360-0. doi : 10.1016/j.cub.2019.10.020