Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Biology

Supervisor

Simon, Anne F.

Abstract

Autism spectrum disorders can be clinically defined in part by impairments of social interactions. Social interactions can be modeled in Drosophila melanogaster with behaviours such as social spacing. Here, I examined the effects of autism-related gene neuroligin 3 on fly social spacing. I hypothesized if neuroligin 3 is mutated or gene expression is targeted for knockdown, then flies will have altered social space in males and females at different ages. Using the social space assay, I found that different mutations to neuroligin 3 change the fly’s behavior, in a mutation and sex-specific manner. Using an antibody against Nlg3, I localized the protein within the mushroom bodies and protocerebral bridge of the fly brain. Using targeted knockdown, I determined that the nlg3 gene in the protocerebral bridge was necessary for proper climbing. The results were inconclusive with regard to an effect on social space.

Summary for Lay Audience

In this research, I am studying one of the geneticists’ favorite model, the vinegar fly a.k.a. the fruit fly (Drosophila melanogaster). Although we do not fly ourselves, comparable behaviours such as movement, sleep, or aggression can be studied. Flies also have social behaviours, for example when a male fly courts a female, or in a group setting, flies will prefer to settle at a specific distance to another fly. Just as humans can have a personal bubble or social space, flies too have a preferred distance to other flies. We can study and learn about this behaviour by looking at the contributing genetic factors or how the brain leads to the decision for creating this personal bubble. Since fruit flies share around 60% of their DNA sequence with us, and 75% of disease-related gene have a counterpart in the fly, we can look at which of these genes alter the fly’s behaviour. If we study genes altering social space behaviour in the fly we can characterize the fundamental function of these genes, and potentially this knowledge could be relevant for human disorders, and possibly allow us to test potential therapies for this disorder. Indeed, there are human disorders, genetically inherited, that are clinically defined by symptoms of impaired social interactions. I am studying one of these genes called neuroligin, which in humans is linked to autism. This family of genes has a conserved function from human to worms, including flies: the protein it encodes facilitates communication between the brain to other parts of the brain or the rest of the body. Here, I show that one of these genes, Drosophila nlg3, affects the fly behaviour. I establish where this gene functions in the fly brain and its presence in those different brain structures can lead to different behavioural outcomes. This new information gives us more insight into the fundamental molecular underpinnings of social interactions, and potentially of autism spectrum disorders.

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