Transgene‐mediated RNA interference defines a novel role for notch in chemosensory startle behavior

Presente, Asaf; Shaw, Susan; Nye, Jeffrey S.; Andres, Andrew J.

doi:10.1002/gene.10149

Cited by 34 publications

(29 citation statements)

References 42 publications

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“…Working N ts1 parental strains were generated from a line bearing a duplication of the Notch locus to limit the accumulation of Notch modifiers. Isolines were chosen based on permissive temperature flight and nonpermissive temperature impairments in flight and longevity, which is consistent with our previously published phenotypes for adult Notch dysfunction (16).…”

Section: Methodsmentioning

confidence: 97%

“…To further test the requirement of Notch in long-term memory, we used another reagent capable of silencing Notch function in a conditional manner. We have developed an inducible Notch RNAi transgene (Ni) that dramatically reduces Notch protein levels to produce a loss-of-function phenotype when assayed in a developmental context (16). This reagent can be used with the upstream activating sequence (UAS)-GAL4 binary expression system, which allows tissue-specific targeting (28) of the RNAi.…”

Section: Rnai-mediated Notch Dysfunction Spares Short-term Memory Andmentioning

confidence: 99%

“…To investigate Notch function in adults, it is necessary to use conditional reagents to avoid developmental phenotypes that may kill the fly or compromise behavior. We used a Notch temperature-sensitive allele (N ts1 ) (15) and RNA interference (RNAi) derived from an inducible transgene (16), in combination with two independent behavioral assays for memory. We show that short-term memory is not impaired by conditional manipulations of Notch, but that Notch is required in adults for long-term memory.…”

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confidence: 99%

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Notch is required for long-term memory in Drosophila

Presente

Boyles

Serway

et al. 2004

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

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126

102

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A role for Notch in the elaboration of existing neural processes is emerging that is distinct from the increasingly well understood function of this gene in binary cell-fate decisions. Several research groups, by using a variety of organisms, have shown that Notch is important in the development of neural ultrastructure. Simultaneously, Presenilin (Psn) was identified both as a key mediator of Notch signaling and as a site of genetic lesions that cause earlyonset Alzheimer's disease. Here we demonstrate that Notch loss of function produces memory deficits in Drosophila melanogaster. The effects are specific to long-term memory, which is thought to depend on ultrastructural remodeling. We propose that Notch plays an important role in the neural plasticity underlying consolidated memory.W hereas the Notch protein plays an important role in binary cell-fate decisions during development (1), it is also present in the adult brain (2, 3). This finding is particularly interesting in adult Drosophila because the CNS is established by eclosion (4). Given that Notch is not needed for cell-fate decisions in the adult brain, its role in this tissue is unclear.Several groups have shown that Notch is important in the arborization of neuritic processes in development. In mammals, Notch regulates arborization of cortical neurons in vivo (5, 6) and in tissue culture (7,8). In Drosophila, the Notch pathway is required for the elaboration of processes in the CNS in the developing third-instar larva (9) and in the embryo (10, 11). Recently, this work has been extended to the analysis of the developing neuromuscular junction, a structure that serves as an accessible model for CNS plasticity. In addition, a Psn-mediated role for Notch is required in the development of neural projections mediating learned thermotaxis in Caenorhabditis elegans (12). Recently (3), we demonstrated that prolonged disruptions in Notch function produced an early lethality and an impairment in the coordinated neuromuscular activity of flight. Accordingly, because Notch clearly is involved in the regulation of neural ultrastructure during development, we investigated the possibility that Notch is also required for memory consolidation, a process believed to require remodeling of existing neurons in adults (13).Drosophila is an ideal organism for studying genes influencing behavioral phenotypes. Advances in our understanding of learning and memory mechanisms have been achieved through genetic, transgenic, and genomic studies in the fly (14). To investigate Notch function in adults, it is necessary to use conditional reagents to avoid developmental phenotypes that may kill the fly or compromise behavior. We used a Notch temperature-sensitive allele (N ts1 ) (15) and RNA interference (RNAi) derived from an inducible transgene (16), in combination with two independent behavioral assays for memory. We show that short-term memory is not impaired by conditional manipulations of Notch, but that Notch is required in adults for long-term memory. MethodsDrosophila Strai...

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Section: Methodsmentioning

confidence: 97%

Section: Rnai-mediated Notch Dysfunction Spares Short-term Memory Andmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Notch is required for long-term memory in Drosophila

Presente

Boyles

Serway

et al. 2004

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

Self Cite

126

102

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“…The 375-bp fragment containing the attB sequence was PCR amplified from pUASTB 22 using primers listed in Supplementary Table 2 online, MM#7 and MM#8. We created pCa4B-UAS::luc and pCa4B-UAS::NotchRNAi by digesting pUAST-luciferase (gift of J. Bai) and pUAST-NotchRNAi 29 with BamHI and cloning each respective fragment into the BamHI site of pCa4B. A gypsyinsulated version of pCa4B called pCa4B2G (pCa4B with 2 Gypsy insulators) was created by PCR amplifying the 341-bp gypsy insulator from a single y 2 fly 44,45 with primers MM#91 and MM#92 (see Supplementary Table 2), digesting the product with SpeI and XbaI and ligating the fragment in sequential steps into the SpeI and XbaI sites of pCa4B.…”

Section: Methodsmentioning

confidence: 99%

“…Toward this end, we took advantage of a hairpin construct against the Notch gene that was previously shown to produce quantifiable wing phenotypes 29 . We integrated this UAS::Notch RNAi construct into three attP landing sites with low basal activity-attP3, attP2 and attP40-that each differ in their ability to drive luciferase in the wing disc (Fig.…”

Section: Global Basal and Inducible Activity At Attp Landing Sitesmentioning

confidence: 99%