Analysis of two P‐element enhancer‐trap insertion lines that show expression in the giant fibre neuron of <i>Drosophila melanogaster</i>

Allen, Marcus; Drummond, James A.; Sweetman, Dylan; Moffat, K.

doi:10.1111/j.1601-183x.2006.00263.x

Cited by 5 publications

(5 citation statements)

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“…2B), whereas mutations that decrease behavioral bang-sensitivity raise the threshold [29], [42]. Examination of kcc RNAi-induced seizure-susceptibility showed that the threshold to evoked seizure-like discharges of experimental A307-GAL4 (driving in a subset of neurons [43], [44]) flies (genotype: A307-GAL4>kcc-RNAi-V ) was about one-fourth that of wild-type and control genotypes (Fig. 2C).…”

Section: Resultsmentioning

confidence: 95%

Modeling Glial Contributions to Seizures and Epileptogenesis: Cation-Chloride Cotransporters in Drosophila melanogaster

2014

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Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl− cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi) of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24–48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl− cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.

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Section: Resultsmentioning

confidence: 95%

Modeling Glial Contributions to Seizures and Epileptogenesis: Cation-Chloride Cotransporters in Drosophila melanogaster

2014

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“…Flies also were tested for suppression using a307-GAL4, a line expressed strongly and specifically in the GF neurons (Allen et al 2007). While no behavioral effect was observed in the para bss1 /+ mutant flies, nor were seizure thresholds increased at room temperature, we saw strong suppression with a307-GAL4 in para bss1 and eas genotypes that were preincubated at 28°before bang testing ( Figure 7C).…”

Section: Electrophysiological Deficits In Shi Ts1 Mutants Indicate Symentioning

confidence: 99%

Disruption of Endocytosis with the Dynamin Mutantshibirets1Suppresses Seizures inDrosophila

et al. 2015

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One challenge in modern medicine is to control epilepsies that do not respond to currently available medications. Since seizures consist of coordinated and high-frequency neural activity, our goal was to disrupt neurotransmission with a synaptic transmission mutant and evaluate its ability to suppress seizures. We found that the mutant shibire, encoding dynamin, suppresses seizure-like activity in multiple seizure-sensitive Drosophila genotypes, one of which resembles human intractable epilepsy in several aspects. Because of the requirement of dynamin in endocytosis, increased temperature in the shi ts1 mutant causes impairment of synaptic vesicle recycling and is associated with suppression of the seizure-like activity. Additionally, we identified the giant fiber neuron as critical in the seizure circuit and sufficient to suppress seizures. Overall, our results implicate mutant dynamin as an effective seizure suppressor, suggesting that targeting or limiting the availability of synaptic vesicles could be an effective and general method of controlling epilepsy disorders.

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“…We used electrophysiology to assay GFS function, which, in combination with morphological analysis, can reveal abnormalities of synaptogenesis during development [4-7,9,11,12,20]. A severe GF-TTMn synaptic phenotype is caused by over-expression of Gl DN ; some flies fail to respond to brain stimulation and those that do respond exhibit a long response latency and show only a single response or poor following to repetitive stimuli ([20]; Figure 4).…”

Section: Resultsmentioning

confidence: 99%

“…Several studies using over-expression of dominant-negative transgenes, or homozygous adult viable mutations, have recently shed light on signaling mechanisms during the formation of the GF-TTMn synapse. These include the receptors Semaphorin 1a and Roundabout [4,5]; the L-1 type cell-adhesion molecule Neuroglian [6]; the endocytotic and ubiquitin machinery [7-10]; the small GTPase DRac1 [11], and the transcription factor Ken [12]. However, the precise mechanisms by which these integrate during synaptogenesis are yet to emerge.…”

Section: Introductionmentioning

confidence: 99%

A modifier screen in the Drosophila eye reveals that aPKC interacts with Glued during central synapse formation

Johns

Allen

2009

BMC Genet

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BackgroundThe Glued gene of Drosophila melanogaster encodes the homologue of the vertebrate p150Glued subunit of dynactin. The Glued1 mutation compromises the dynein-dynactin retrograde motor complex and causes disruptions to the adult eye and the CNS, including sensory neurons and the formation of the giant fiber system neural circuit.ResultsWe performed a 2-stage genetic screen to identify mutations that modified phenotypes caused by over-expression of a dominant-negative Glued protein. We screened over 34,000 flies and isolated 41 mutations that enhanced or suppressed an eye phenotype. Of these, 12 were assayed for interactions in the giant fiber system by which they altered a giant fiber morphological phenotype and/or altered synaptic function between the giant fiber and the tergotrochanteral muscle motorneuron. Six showed interactions including a new allele of atypical protein kinase C (aPKC). We show that this cell polarity regulator interacts with Glued during central synapse formation. We have mapped the five other interacting mutations to discrete chromosomal regions.ConclusionOur results show that an efficient way to screen for genes involved in central synapse formation is to use a two-step strategy in which a screen for altered eye morphology precedes the analysis of central synaptogenesis. This has highlighted a role for aPKC in the formation of an identified central synapse.

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Analysis of two P‐element enhancer‐trap insertion lines that show expression in the giant fibre neuron of Drosophila melanogaster

Cited by 5 publications

References 64 publications

Modeling Glial Contributions to Seizures and Epileptogenesis: Cation-Chloride Cotransporters in Drosophila melanogaster

Modeling Glial Contributions to Seizures and Epileptogenesis: Cation-Chloride Cotransporters in Drosophila melanogaster

Disruption of Endocytosis with the Dynamin Mutantshibirets1Suppresses Seizures inDrosophila

A modifier screen in the Drosophila eye reveals that aPKC interacts with Glued during central synapse formation

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