Abnormal Social Interactions in a Drosophila Mutant of an Autism Candidate Gene: Neuroligin 3

Social interactions are typically impaired in neuropsychiatric disorders such as autism, for which the genetic underpinnings are very complex. Social interactions can be modeled by analysis of behaviors, including social spacing, sociability, and aggression, in simpler organisms such as Drosophila melanogaster. Here, we examined the effects of mutants of the autism-related gene neuroligin 3 (nlg3) on fly social and non-social behaviors. Startled-induced negative geotaxis is affected by a loss of function nlg3 mutation. Social space and aggression are also altered in a sex- and social-experience-specific manner in nlg3 mutant flies. In light of the conserved roles that neuroligins play in social behavior, our results offer insight into the regulation of social behavior in other organisms, including humans.

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Sex-Specific Social Behavior and Amygdala Proteomic Deficits in Foxp2+/− Mutant Mice

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2021.706079 ◽

2021 ◽

Vol 15 ◽

Author(s):

Maria Jesus Herrero ◽

Li Wang ◽

David Hernandez-Pineda ◽

Payal Banerjee ◽

Heidi Y. Matos ◽

...

Keyword(s):

Social Behavior ◽

Social Interactions ◽

Social Behaviors ◽

Autism Spectrum ◽

Loss Of Function ◽

Neuronal Communication ◽

Males And Females ◽

Spectrum Disorders ◽

Encoding Gene ◽

Dopamine Signaling

In humans, mutations in the transcription factor encoding gene, FOXP2, are associated with language and Autism Spectrum Disorders (ASD), the latter characterized by deficits in social interactions. However, little is known regarding the function of Foxp2 in male or female social behavior. Our previous studies in mice revealed high expression of Foxp2 within the medial subnucleus of the amygdala (MeA), a limbic brain region highly implicated in innate social behaviors such as mating, aggression, and parental care. Here, using a comprehensive panel of behavioral tests in male and female Foxp2+/– heterozygous mice, we investigated the role Foxp2 plays in MeA-linked innate social behaviors. We reveal significant deficits in olfactory processing, social interaction, mating, aggressive, and parental behaviors. Interestingly, some of these deficits are displayed in a sex-specific manner. To examine the consequences of Foxp2 loss of function specifically in the MeA, we conducted a proteomic analysis of microdissected MeA tissue. This analyses revealed putative sex differences expression of a host of proteins implicated in neuronal communication, connectivity, and dopamine signaling. Consistent with this, we discovered that MeA Foxp2-lineage cells were responsive to dopamine with differences between males and females. Thus, our findings reveal a central and sex-specific role for Foxp2 in social behavior and MeA function.

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Modulation of social space by dopamine in Drosophila melanogaster, but no effect on the avoidance of the Drosophila stress odorant

Biology Letters ◽

10.1098/rsbl.2017.0369 ◽

2017 ◽

Vol 13 (8) ◽

pp. 20170369 ◽

Cited By ~ 15

Author(s):

Robert W. Fernandez ◽

Adesanya A. Akinleye ◽

Marat Nurilov ◽

Omar Feliciano ◽

Matthew Lollar ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Social Interactions ◽

Social Group ◽

Social Space ◽

Social Cues ◽

Social Spacing ◽

Pharmacological Manipulations

Appropriate response to others is necessary for social interactions. Yet little is known about how neurotransmitters regulate attractive and repulsive social cues. Using genetic and pharmacological manipulations in Drosophila melanogaster , we show that dopamine is contributing the response to others in a social group, specifically, social spacing, but not the avoidance of odours released by stressed flies (dSO). Interestingly, this dopamine-mediated behaviour is prominent only in the day-time, and its effect varies depending on tissue, sex and type of manipulation. Furthermore, alteration of dopamine levels has no effect on dSO avoidance regardless of sex, which suggests that a different neurotransmitter regulates this response.

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Antibiotics increase aggression behavior and aggression-related pheromones and receptors in Drosophila melanogaster

10.1101/2020.09.22.307777 ◽

2020 ◽

Author(s):

Michal Grinberg ◽

Hadar Neuman ◽

Oren Ziv ◽

Sondra Turjeman ◽

Rita Nosenko ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Social Behavior ◽

Gut Microbiota ◽

Aggressive Behavior ◽

Social Interactions ◽

Bacterial Species ◽

Environmental Cues ◽

Aggressive Behaviors ◽

Aggression Behavior

AbstractAggression is a behavior common in most species; it is controlled by internal and external drivers, including hormones, environmental cues, and social interactions, and underlying pathways are understood in a broad range of species. To date, though, effects of gut microbiota on aggression in the context of gut-brain communication and social behavior have not been elucidated. We examine how manipulation of Drosophila melanogaster microbiota affect aggression as well as the pathways that underly the behavior in this species. Flies treated with antibiotics exhibited significantly more aggressive behaviors. Furthermore, they had higher levels of vCA and (Z)-9 Tricosene, pheromones associated with aggression in flies, as well as higher expression of the relevant pheromone receptors and transporters OR67d, OR83b, GR32a, and LUSH. These findings suggest that aggressive behavior is, at least in part, mediated by bacterial species in flies.

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The switching mechanisms of social network densification

Scientific Reports ◽

10.1038/s41598-021-82432-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Teruyoshi Kobayashi ◽

Mathieu Génois

Keyword(s):

Social Networks ◽

Social Network ◽

Social Context ◽

Social Interactions ◽

Regime Switching ◽

Face To Face ◽

The Social ◽

Switching Property ◽

Distinctive Type ◽

Insight Into

AbstractDensification and sparsification of social networks are attributed to two fundamental mechanisms: a change in the population in the system, and/or a change in the chances that people in the system are connected. In theory, each of these mechanisms generates a distinctive type of densification scaling, but in reality both types are generally mixed. Here, we develop a Bayesian statistical method to identify the extent to which each of these mechanisms is at play at a given point in time, taking the mixed densification scaling as input. We apply the method to networks of face-to-face interactions of individuals and reveal that the main mechanism that causes densification and sparsification occasionally switches, the frequency of which depending on the social context. The proposed method uncovers an inherent regime-switching property of network dynamics, which will provide a new insight into the mechanics behind evolving social interactions.

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Aberrant aggressive behavior in a mouse model of Angelman syndrome

Scientific Reports ◽

10.1038/s41598-020-79984-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lilach Simchi ◽

Hanoch Kaphzan

Keyword(s):

Social Behavior ◽

Mouse Model ◽

Aggressive Behavior ◽

Social Interactions ◽

Angelman Syndrome ◽

Case Reports ◽

Neurodevelopmental Disorder ◽

Therapeutic Interventions ◽

Affiliative Behavior ◽

Severe Difficulty

AbstractAngelman syndrome (AS) is a genetic neurodevelopmental disorder due to the absence of the E3-ligase protein, UBE3A. Inappropriate social interactions, usually hyper-sociability, is a part of that syndrome. In addition, clinical surveys and case reports describe aggressive behavior in AS individuals as a severe difficulty for caretakers. A mouse model for AS recapitulates most of the human AS phenotypes. However, very few studies utilized this mouse model for investigating affiliative social behavior, and not even a single study examined aggressive behavior. Hence, the aim of the herein study was to examine affiliative and aggressive social behavior. For that, we utilized a battery of behavioral paradigms, and performed detailed analyses of these behaviors. AS mice exhibited a unique characteristic of reduced habituation towards a social stimulus in comparison to their wild-type (WT) littermates. However, overall there were no additional marked differences in affiliative social behavior. In contrast to the mild changes in affiliative behavior, there was a striking enhanced aggression in the AS mice compared to their WT littermates. The herein findings emphasize the use of AS mouse model in characterizing and measuring inappropriate aggressive behavior, and suggests these as tools for investigating therapeutic interventions aimed at attenuating aggressive behavior.

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Somatic production of reactive oxygen species does not predict its production in sperm cells across Drosophila melanogaster lines

BMC Research Notes ◽

10.1186/s13104-021-05550-7 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Biz R. Turnell ◽

Luisa Kumpitsch ◽

Anne-Cécile Ribou ◽

Klaus Reinhardt

Keyword(s):

Reactive Oxygen Species ◽

Drosophila Melanogaster ◽

Reactive Oxygen ◽

Future Research ◽

Ros Production ◽

Oxygen Species ◽

Loss Of Function ◽

Wild Type ◽

Ros Scavenging ◽

Transport Chain

Abstract Objective Sperm ageing has major evolutionary implications but has received comparatively little attention. Ageing in sperm and other cells is driven largely by oxidative damage from reactive oxygen species (ROS) generated by the mitochondria. Rates of organismal ageing differ across species and are theorized to be linked to somatic ROS levels. However, it is unknown whether sperm ageing rates are correlated with organismal ageing rates. Here, we investigate this question by comparing sperm ROS production in four lines of Drosophila melanogaster that have previously been shown to differ in somatic mitochondrial ROS production, including two commonly used wild-type lines and two lines with genetic modifications standardly used in ageing research. Results Somatic ROS production was previously shown to be lower in wild-type Oregon-R than in wild-type Dahomey flies; decreased by the expression of alternative oxidase (AOX), a protein that shortens the electron transport chain; and increased by a loss-of-function mutation in dj-1β, a gene involved in ROS scavenging. Contrary to predictions, we found no differences among these four lines in the rate of sperm ROS production. We discuss the implications of our results, the limitations of our study, and possible directions for future research.

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The Effectiveness of Multi-Label Classification and Multi-Output Regression in Social Trait Recognition

Sensors ◽

10.3390/s21124127 ◽

2021 ◽

Vol 21 (12) ◽

pp. 4127

Author(s):

Will Farlessyost ◽

Kelsey-Ryan Grant ◽

Sara R. Davis ◽

David Feil-Seifer ◽

Emily M. Hand

Keyword(s):

Social Interactions ◽

First Impressions ◽

Social Traits ◽

Judicial Proceedings ◽

Facial Attributes ◽

Future Work ◽

Automated Methods ◽

Insight Into ◽

Social Trait ◽

Better Than

First impressions make up an integral part of our interactions with other humans by providing an instantaneous judgment of the trustworthiness, dominance and attractiveness of an individual prior to engaging in any other form of interaction. Unfortunately, this can lead to unintentional bias in situations that have serious consequences, whether it be in judicial proceedings, career advancement, or politics. The ability to automatically recognize social traits presents a number of highly useful applications: from minimizing bias in social interactions to providing insight into how our own facial attributes are interpreted by others. However, while first impressions are well-studied in the field of psychology, automated methods for predicting social traits are largely non-existent. In this work, we demonstrate the feasibility of two automated approaches—multi-label classification (MLC) and multi-output regression (MOR)—for first impression recognition from faces. We demonstrate that both approaches are able to predict social traits with better than chance accuracy, but there is still significant room for improvement. We evaluate ethical concerns and detail application areas for future work in this direction.

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Trans-acting Factors Required for Inclusion of Regulated Exons in the Ultrabithorax mRNAs of Drosophila melanogaster

Genetics ◽

10.1093/genetics/151.4.1517 ◽

1999 ◽

Vol 151 (4) ◽

pp. 1517-1529 ◽

Cited By ~ 2

Author(s):

James M Burnette ◽

Allyson R Hatton ◽

A Javier Lopez

Keyword(s):

Drosophila Melanogaster ◽

Alternative Splicing ◽

P Element ◽

Splicing Factors ◽

Loss Of Function ◽

Large Collection ◽

Splicing Pattern ◽

Alternatively Spliced ◽

Hypomorphic Alleles

Abstract Alternatively spliced Ultrabithorax mRNAs differ by the presence of internal exons mI and mII. Two approaches were used to identify trans-acting factors required for inclusion of these cassette exons. First, mutations in a set of genes implicated in the control of other alternative splicing decisions were tested for dominant effects on the Ubx alternative splicing pattern. To identify additional genes involved in regulation of Ubx splicing, a large collection of deficiencies was tested first for dominant enhancement of the haploinsufficient Ubx haltere phenotype and second for effects on the splicing pattern. Inclusion of the cassette exons in Ubx mRNAs was reduced strongly in heterozygotes for hypomorphic alleles of hrp48, which encodes a member of the hnRNP A/B family and is implicated in control of P-element splicing. Significant reductions of mI and mII inclusion were also observed in heterozygotes for loss-of-function alleles of virilizer, fl(2)d, and crooked neck. The products of virilizer and fl(2)d are also required for Sxl autoregulation at the level of splicing; crooked neck encodes a protein with structural similarities to yeast-splicing factors Prp39p and Prp42p. Deletion of at least five other loci caused significant reductions in the inclusion of mI and/or mII. Possible roles of identified factors are discussed in the context of the resplicing strategy for generation of alternative Ubx mRNAs.

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Cross-Species RNAi Rescue Platform in Drosophila melanogaster

Genetics ◽

10.1534/genetics.109.106567 ◽

2009 ◽

Vol 183 (3) ◽

pp. 1165-1173 ◽

Cited By ~ 34

Author(s):

Shu Kondo ◽

Matthew Booker ◽

Norbert Perrimon

Keyword(s):

Cell Culture ◽

Drosophila Melanogaster ◽

Large Scale ◽

Transgenic Animals ◽

Selection Marker ◽

Bacterial Artificial Chromosomes ◽

Loss Of Function ◽

Artificial Chromosomes ◽

Target Effects

RNAi-mediated gene knockdown in Drosophila melanogaster is a powerful method to analyze loss-of-function phenotypes both in cell culture and in vivo. However, it has also become clear that false positives caused by off-target effects are prevalent, requiring careful validation of RNAi-induced phenotypes. The most rigorous proof that an RNAi-induced phenotype is due to loss of its intended target is to rescue the phenotype by a transgene impervious to RNAi. For large-scale validations in the mouse and Caenorhabditis elegans, this has been accomplished by using bacterial artificial chromosomes (BACs) of related species. However, in Drosophila, this approach is not feasible because transformation of large BACs is inefficient. We have therefore developed a general RNAi rescue approach for Drosophila that employs Cre/loxP-mediated recombination to rapidly retrofit existing fosmid clones into rescue constructs. Retrofitted fosmid clones carry a selection marker and a phiC31 attB site, which facilitates the production of transgenic animals. Here, we describe our approach and demonstrate proof-of-principle experiments showing that D. pseudoobscura fosmids can successfully rescue RNAi-induced phenotypes in D. melanogaster, both in cell culture and in vivo. Altogether, the tools and method that we have developed provide a gold standard for validation of Drosophila RNAi experiments.

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Cytoplasmic dynein (ddlc1) mutations cause morphogenetic defects and apoptotic cell death in Drosophila melanogaster.

Molecular and Cellular Biology ◽

10.1128/mcb.16.5.1966 ◽

1996 ◽

Vol 16 (5) ◽

pp. 1966-1977 ◽

Cited By ~ 104

Author(s):

T Dick ◽

K Ray ◽

H K Salz ◽

W Chia

Keyword(s):

Drosophila Melanogaster ◽

Light Chain ◽

Blot Analysis ◽

Cytoplasmic Dynein ◽

P Element ◽

Female Sterility ◽

Dynein Light Chain ◽

Loss Of Function ◽

Light Chain Gene

We report the molecular and genetic characterization of the cytoplasmic dynein light-chain gene, ddlc1, from Drosophila melanogaster. ddlc1 encodes the first cytoplasmic dynein light chain identified, and its genetic analysis represents the first in vivo characterization of cytoplasmic dynein function in higher eucaryotes. The ddlc1 gene maps to 4E1-2 and encodes an 89-amino-acid polypeptide with a high similarity to the axonemal 8-kDa outer-arm dynein light chain from Chlamydomonas flagella. Developmental Northern (RNA) blot analysis and ovary and embryo RNA in situ hybridizations indicate that the ddlc1 gene is expressed ubiquitously. Anti-DDLC1 antibody analyses show that the DDLC1 protein is localized in the cytoplasm. P-element-induced partial-loss-of-function mutations cause pleiotropic morphogenetic defects in bristle and wing development, as well as in oogenesis, and hence result in female sterility. The morphological abnormalities found in the ovaries are always associated with a loss of cellular shape and structure, as visualized by a disorganization of the actin cytoskeleton. Total-loss-of-function mutations cause lethality. A large proportion of mutant animals degenerate during embryogenesis, and the dying cells show morphological changes characteristic of apoptosis, namely, cell and nuclear condensation and fragmentation, as well as DNA degradation. Cloning of the human homolog of the ddlc1 gene, hdlc1, demonstrates that the dynein light-chain 1 is highly conserved in flies and humans. Northern blot analysis and epitope tagging show that the hdlc1 gene is ubiquitously expressed and that the human dynein light chain 1 is localized in the cytoplasm. hdlc1 maps to 14q24.

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