100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future

Bellen, Hugo J.; Tong, Chao; Tsuda, Hiroshi

doi:10.1038/nrn2839

Cited by 396 publications

(307 citation statements)

References 222 publications

(178 reference statements)

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“…Drosophila has been used extensively for investigating fundamental biological processes, such as cell death (Hay et al 2004;Hay and Guo 2006), as well as cell proliferation, growth, and migration (for review, see Bellen et al 2010). In addition, flies display complex behaviors such as circadian rhythms, learning and memory, sleep, and aggression (Bellen et al 2010). Some of these were thought to be exclusive to humans, and studies now suggest that the genetic bases of these behaviors are conserved in humans.…”

Section: The Advantages Of Using Drosophila As a Model System To Studmentioning

confidence: 99%

Drosophila as a Model to Study Mitochondrial Dysfunction in Parkinson's Disease

Guo¹

2012

Cold Spring Harbor Perspectives in Medicine

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Identification of single gene mutations that lead to inherited forms of Parkinson's disease (PD) has provided strong impetus for the use of animal models to study normal functions of these "PD genes" and the cellular defects that occur in the presence of pathogenic PD mutations. Drosophila has emerged as an effective model in PD-related gene studies. Important insights into the cellular basis of PD pathogenesis include the demonstration that two PD genes, PINK1 and parkin, function in a common pathway, with PINK1 positively regulating parkin, to control mitochondrial integrity and maintenance. This is accomplished through regulation of mitochondrial fission/fusion dynamics. Subsequent observations in both fly and mammalian systems showed that these proteins are important for sensing mitochondrial damage and recruiting damaged mitochondria to the quality-control machinery for subsequent removal. Here, I begin by reviewing the opportunities and challenges to understanding PD pathogenesis and developing new therapies. I then review the unique tools and technologies available in Drosophila for studying PD genes. Subsequently, I review lessons that we have learned from studies in Drosophila, emphasizing the PINK1/parkin pathway, as well as studies of DJ-1 and Omi/HtrA2, two additional genes associated with PD implicated in regulation of mitochondrial function. I end by discussing how Drosophila can be used to further probe the functions of PINK1 and parkin, and the regulation of mitochondrial quality more generally. In additional to PD, defects in mitochondrial function are associated with normal aging and with many diseases of aging. Thus, insights gained from the studies of mitochondrial dynamics and quality control in Drosophila are likely to be of general significance. Parkinson's disease (PD) is the second most common neurodegenerative disorder, with a prevalence second only to that of Alzheimer's disease. There is no cure or treatment that can halt disease progression. A primary pathological hallmark of the disease is degeneration of multiple neuronal types including, most notably, dopaminergic neurons in the substantia nigra of the midbrain (Dauer and Przedborski 2003;Shulman et al. 2011). However, pathology of many non-dopaminergic neurons including olfactory and brain stem neurons predates that of DA neurons (Braak et al. 2003). Patients with PD present with characteristic "motor symptoms," such as resting tremor, slowness of movement, rigidity, postural instability, and gait difficulty. Although the mainstay of current medical treatment for PD is dopamine replacement, this is not very satisfying. First, the dopamine replacement only alleviates some of the motor symptoms (does not help gait problems), becomes less effective over time, and is often associated with intolerable side effects. Second, PD patients also present with a combination of non-motor symptoms (Simuni and Sethi 2008) including dementia, which occurs in more than one-third of patients; psychiatric symptoms such as depression, anxiety, and ob...

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Section: The Advantages Of Using Drosophila As a Model System To Studmentioning

confidence: 99%

Drosophila as a Model to Study Mitochondrial Dysfunction in Parkinson's Disease

Guo¹

2012

Cold Spring Harbor Perspectives in Medicine

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“…Network dynamics seem to be consistent at varying densities. Networks were evaluated at 12.5%, 20%, 25%, 50%, and 75% density to determine consistency of network dynamics (17,27,33,66, and 99 unique directed interactions, respectively; see text). Z scores were based on 500 simulations, which preserved the in-and out-degree of the iterative networks.…”

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confidence: 99%

Social structures depend on innate determinants and chemosensory processing inDrosophila

Schneider

Dickinson

Levine

2012

Proc. Natl. Acad. Sci. U.S.A.

174

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Flies display transient social interactions in groups. However, whether fly-fly interactions are stochastic or structured remains unknown. We hypothesized that groups of flies exhibit patterns of social dynamics that would manifest as nonrandom social interaction networks. To test this, we applied a machine vision system to track the position and orientation of flies in an arena and designed a classifier to detect interactions between pairs of flies. We show that the vinegar fly, Drosophila melanogaster, forms nonrandom social interaction networks, distinct from virtual network controls (constructed from the intersections of individual locomotor trajectories). In addition, the formation of interaction networks depends on chemosensory cues. Gustatory mutants form networks that cannot be distinguished from their virtual network controls. Olfactory mutants form networks that are greatly disrupted compared with control flies. Different wild-type strains form social interaction networks with quantitatively different properties, suggesting that the genes that influence this network phenotype vary across and within wild-type populations. We have established a paradigm for studying social behaviors at a group level in Drosophila and expect that a genetic dissection of this phenomenon will identify conserved molecular mechanisms of social organization in other species.social network | emergent phenotypes | complex systems F lies engage in a variety of social behaviors that include courtship, aggression, mating, and egg-laying (1-5). Recent studies also indicate that individuals have the ability to recognize others (6) and regulate their behavior according to group membership (7). The composition of such Drosophila groups forms a social environment that influences gene transcription, pheromone displays, and mating frequency among group members (7-9). However, the genetic and sensory determinants that underlie these observations are unknown.To explore the possibility that Drosophila form organized social interaction networks (SINs), we quantified interactions formed by pairs of individuals within groups of 12 flies of the same sex placed in a circular arena (10). Using video sequences, three classes of behavior suggesting social interactions were identified: frontal approach, rear approach, and social preening (also known as "grooming," in which a fly rubs its legs together, or uses the leg(s) to rub its own wings, head, or abdomen). Social preening has been previously associated with social interactions in Drosophila (11, 12). These behaviors were verified in detail using video sequences captured at high spatial and temporal resolution (Movie S1). Inspection of video sequences indicated that these classes of behaviors often involve physical contact between the fore-and middle legs of the interacting flies, and these were scored to evaluate their relative frequency of occurrence (Table S1). Drosophila legs harbor both touch-and tastesensitive sensillae (13), suggesting that flies might exchange somatosensory and gustatory ...

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“…This proof copy is the copyright property of the publisher and is confidential until formal publication. Second, 100 years of intense research has led to excellent conceptual understanding of fundamental biology in Drosophila (Bate & Martínez-Arias, 1993;Bellen, Tong, & Tsuda, 2010;Demerec, 1950;Kohler, 1994). This provides a prolific context in which to perform in vivo experiments, further fueled by countless genetic tools, usually readily available (all listed in FlyBase and many obtainable from resource centers; Cherbas & Gong, 2014;Matthews, Kaufman, & Gelbart, 2005;McQuilton et al, 2012;St.…”

Section: Article In Pressmentioning

confidence: 99%

“…Such studies can capitalize on efficient combinatorial genetics available in the fly, an excellent infrastructure providing easy access to information and a rich pool of molecular tools, as well as the ease of in vivo work complementary to culture studies. Notably, understanding gained form studies on Shot can instruct work in vertebrates or mammals, thus accelerating research and often revealing a high degree of mechanistic conservation (Bellen et al, 2010). …”

Section: Conclusion P0220mentioning

confidence: 99%