Central Adaptation to Odorants Depends on PI3K Levels in Local Interneurons of the Antennal Lobe

Acebes, Ángel; Devaud, Jean-Marc; Arnés, Mercedes; Ferrús, Alberto

doi:10.1523/jneurosci.2921-11.2012

Cited by 16 publications

(15 citation statements)

References 31 publications

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“…To verify if some enhancers are less susceptible to ectopic activity than others, we searched for Gal4 constructs whose activity in the mature adult brain is restricted to the brain. c105- Gal4 is active in a small number of cells during pupariation and adulthood [8] (see figure 4 g – i and electronic supplementary material, table S1) and GH298- Gal4 is active in local olfactory interneurons from larva and adult brain [31,32] (see figure 4 j – l and electronic supplementary material, table S1). Our G-TRACE data show that there are some GFP positive cells dispersed in the adult brain and two groups of cells that had transient activity of the enhancer c105 (figure 4 g – i , arrowheads).…”

Section: Resultsmentioning

confidence: 99%

Drosophilaenhancer-Gal4 lines show ectopic expression during development

Casas‐Tintó¹,

Arnés²,

Ferrús³

2017

R. Soc. open sci.

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In Drosophila melanogaster the most widely used technique to drive gene expression is the binary UAS/Gal4 system. We show here that a set of nervous system specific enhancers (elav, D42/Toll-6, OK6/RapGAP1) display ectopic activity in epithelial tissues during development, which is seldom considered in experimental studies. This ectopic activity is variable, unstable and influenced by the primary sequence of the enhancer and the insertion site in the chromosome. In addition, the ectopic activity is independent of the protein expressed, Gal4, as it is reproduced also with the expression of Gal80. Another enhancer, LN2 from the sex lethal (Sxl) gene, shows sex-dependent features in its ectopic expression. Feminization of LN2 expressing males does not alter the male specific pattern indicating that the sexual dimorphism of LN2 expression is an intrinsic feature of this enhancer. Other X chromosome enhancers corresponding to genes not related to sex determination do not show sexual dimorphism in their ectopic expressions. Although variable and unstable, the ectopic activation of enhancer-Gal4 lines seems to be regulated in terms of tissue and intensity. To characterize the full domain of expression of enhancer-Gal4 constructs is relevant for the design of transgenic animal models and biotechnology tools, as well as for the correct interpretation of developmental and behavioural studies in which Gal4 lines are used.

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Section: Resultsmentioning

confidence: 99%

Drosophilaenhancer-Gal4 lines show ectopic expression during development

Casas‐Tintó¹,

Arnés²,

Ferrús³

2017

R. Soc. open sci.

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“…Activation/inhibition of PI3K or downstream elements of this pathway coherently regulate the number of synapses [ 28 – 29 ]. While the overactivation of PI3K-AKT signaling results in functional supernumerary synapses both in Drosophila and mammals [ 28 – 30 ], the overexpression of GSK3 causes a reduction of synapse number [ 28 , 31 – 32 ]. The pathway includes also the Jun kinase/AP-1 and Wnt signaling which are modulated by GSK3 [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

GSK3β Inhibition Promotes Synaptogenesis in Drosophila and Mammalian Neurons

et al. 2015

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The PI3K-dependent activation of AKT results in the inhibition of GSK3β in most signaling pathways. These kinases regulate multiple neuronal processes including the control of synapse number as shown for Drosophila and rodents. Alzheimer disease’s patients exhibit high levels of circulating GSK3β and, consequently, pharmacological strategies based on GSK3β antagonists have been designed. The approach, however, has yielded inconclusive results so far. Here, we carried out a comparative study in Drosophila and rats addressing the role of GSK3β in synaptogenesis. In flies, the genetic inhibition of the shaggy-encoded GSK3β increases the number of synapses, while its upregulation leads to synapse loss. Likewise, in three weeks cultured rat hippocampal neurons, the pharmacological inhibition of GSK3β increases synapse density and Synapsin expression. However, experiments on younger cultures (12 days) yielded an opposite effect, a reduction of synapse density. This unexpected finding seems to unveil an age- and dosage-dependent differential response of mammalian neurons to the stimulation/inhibition of GSK3β, a feature that must be considered in the context of human adult neurogenesis and pharmacological treatments for Alzheimer’s disease based on GSK3β antagonists.

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“…Work in animal models has revealed that PTEN null mutant mice exhibit embryonic lethality, while the heterozygotes are highly susceptible to tumors [60]. Mammalian primary neuron cultures and Drosophila null mutants of PTEN show extensive dendritic arborization, which highlights the role of the PI3K/AKT/mTOR pathway in the regulation of neuronal growth [61,62]. Accordingly with the relationship between neuronal overgrowth and ASD, brain-specific conditional PTEN null mice develop dendritic hypertrophy, increased spine density and progressive macrocephaly confined to the affected brain areas.…”

Section: Ptenmentioning

confidence: 99%

The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia

Enriquez-barreto¹,

Morales²

2016

MCT

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This review is focused in PI3K’s involvement in two widespread mental disorders: Autism and Schizophrenia. A largebody of evidence points to synaptic dysfunction as a cause of these diseases, either during the initial phases ofbrain synaptic circuit’s development or later modulating synaptic function and plasticity. Autism related disordersand Schizophrenia are complex genetic conditions in which the identification of gene markers has proved difficult,although the existence of single-gene mutations with a high prevalence in both diseases offers insight into the roleof the PI3K signaling pathway. In the brain, components of the PI3K pathway regulate synaptic formation and plasticity;thus, disruption of this pathway leads to synapse dysfunction and pathological behaviors. Here, we recapitulate recentevidences that demonstrate the imbalance of several PI3K elements as leading causes of Autism and Schizophrenia,together with the plausible new pharmacological paths targeting this signaling pathway.

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Central Adaptation to Odorants Depends on PI3K Levels in Local Interneurons of the Antennal Lobe

Cited by 16 publications

References 31 publications

Drosophilaenhancer-Gal4 lines show ectopic expression during development

Drosophilaenhancer-Gal4 lines show ectopic expression during development

GSK3β Inhibition Promotes Synaptogenesis in Drosophila and Mammalian Neurons

The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia

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