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Modeling Mental Disorders in Fruit Flies

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Fruit flies (Drosophila melanogaster) have been used as a promising model for understanding cellular and molecular mechanisms of diverse human genetic diseases including neuronal degeneration. The vast array of transgenic techniques in Drosophila enables in-depth analyses of disease gene functions. This can ...

Fruit flies (Drosophila melanogaster) have been used as a promising model for understanding cellular and molecular mechanisms of diverse human genetic diseases including neuronal degeneration. The vast array of transgenic techniques in Drosophila enables in-depth analyses of disease gene functions. This can be done not only through conventional loss-of-function approaches, but also through gain-of-function approaches which drive constructs of exogenous genes, such as human disease genes, in a targeted set of neurons in the fly brain at diverse and controlled developmental stages. However, for the analysis of biological mechanisms relevant to mental disorders, genetic studies using fruit flies involve a number of empirical and theoretical complications. The major challenge lies in the strategies to dissect psychiatric symptoms that are considered to be specific to human patients. Thus, animal models would not be directly applicable for phenocopying many psychological conditions such as hallucination, delusion, thought distortion and other complex mental representations. The lack of objective biological markers sets another challenge in modeling mental diseases using animals in general. Nevertheless, mechanistic and etiological approaches focusing on endophenotypes, biological alterations underlying or often preceding the psychiatric symptoms, have been conducted for diverse mental disorders although major efforts have been limited to rodent models so far. On the other hand, recent advancements in human genetics have paved the way for systematic genome-wide studies leading to the identification of a large number of gene loci that are either associated with specific mental conditions or are familiarly transmitted with diverse psychiatric abnormalities. Fortunately, the majorities of the genes identified in such studies are evolutionarily conserved and can be found in the fruit fly genome. We thus envisage an emerging opportunity for rapid advancement of molecular psychiatry via convergence of human psychiatric genetics and Drosophila neurogenetics. Such cross-phylum efforts will certainly facilitate the identification of novel risk factors and molecular cellular processes that underlie the pathophysiology of mental illnesses, ultimately translating into novel mechanism-based treatments. In this topic, we aim to overview the emerging field of Drosophila psychogenetics with cutting-edge applications of fruit flies to molecular genetic studies of mental disorders including autism spectrum disorder, bipolar disorder and schizophrenia.


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