nalyot, a Mutation of the Drosophila Myb-Related Adf1 Transcription Factor, Disrupts Synapse Formation and Olfactory Memory

DeZazzo, J D; Sandstrom, David J.; Belle, Steve de; Velinzon, Klara; Smith, Patrick; Grady, Lori; DelVecchio, Maria; Ramaswami, Mani; Tully, Tim

doi:10.1016/s0896-6273(00)00016-7

Cited by 70 publications

(56 citation statements)

References 43 publications

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“…The specificity of the defect to spaced training suggests that, similar to UBE3A mutant mice, dube3a mutant flies learn as well but cannot form LTMs as well as WT flies. Because LTM requires particular transcription factors and protein synthesis (37)(38)(39), Dube3a activity may be involved in regulation of gene expression. were entrained to a 12 h:12 h, light:dark cycle for 3 d before placing them in locomotor activity monitors that record the frequency with which a fly crosses an infrared beam passed through the chamber (40).…”

Section: Flies With Dube3a Mutations Are Defective In Long-term Memorymentioning

confidence: 99%

A Drosophila model for Angelman syndrome

Bolduc

Bell

et al. 2008

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

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Angelman syndrome is a neurological disorder whose symptoms include severe mental retardation, loss of motor coordination, and sleep disturbances. The disease is caused by a loss of function of UBE3A, which encodes a HECT-domain ubiquitin ligase. Here, we generate a Drosophila model for the disease. The results of several experiments show that the functions of human UBE3A and its fly counterpart, dube3a, are similar. First, expression of Dube3a is enriched in the Drosophila nervous system, including mushroom bodies, the seat of learning and memory. Second, we have generated dube3a null mutants, and they appear normal externally, but display abnormal locomotive behavior and circadian rhythms, and defective long-term memory. Third, flies that overexpress Dube3a in the nervous system also display locomotion defects, dependent on the ubiquitin ligase activity. Finally, missense mutations in UBE3A alleles of Angelman syndrome patients alter amino acid residues conserved in the fly protein, and when introduced into dube3a, behave as loss-of-function mutations. The simplest model for Angelman syndrome is that in the absence of UBE3A, particular substrates fail to be ubiquitinated and proteasomally degraded, accumulate in the brain, and interfere with brain function. We have generated flies useful for genetic screens to identify Dube3a substrates. These flies overexpress Dube3a in the eye or wing and display morphological abnormalities, dependent on the critical catalytic cysteine. We conclude that dube3a mutants are a valid model for Angelman syndrome, with great potential for identifying the elusive UBE3A substrates relevant to the disease.

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Section: Flies With Dube3a Mutations Are Defective In Long-term Memorymentioning

confidence: 99%

A Drosophila model for Angelman syndrome

Bolduc

Bell

et al. 2008

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

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“…The Western blot in Fig. 3 was repeated and also probed with a polyclonal ADF-1 antibody (14) to confirm that all lanes were loaded and transferred equally (data not shown).…”

Section: Construction Of the Rtta-alt And Rtta-m2-alt Genes And Transmentioning

confidence: 99%

“…Embryonic immunocytochemistry was performed as described (14,15). Concentrated luciferase hybridoma supernatant was diluted 1:50 and preadsorbed against 0-to 18-h wild-type embryos.…”

Section: Construction Of the Rtta-alt And Rtta-m2-alt Genes And Transmentioning

confidence: 99%

“…The secondary antibody was an horseradish peroxidase-conjugated goat anti-mouse diluted to a final concentration of 1:500 (Jackson ImmunoResearch). Ni-diaminobenzidine-peroxidase was used to visualize immune complexes as described (14). Wandering third-instar larvae were collected and washed in PBS before being dissected in 4% paraformaldehyde (PBS).…”

Section: Construction Of the Rtta-alt And Rtta-m2-alt Genes And Transmentioning

confidence: 99%

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Tetracycline-inducible systems for Drosophila

Stebbins

Urlinger

Byrne

et al. 2001

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

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Since their inception, tetracycline (Tet)-inducible systems have become the method of choice for transgenic research. The Tet-Off systems have a number of advantages, including robust target induction using a relatively benign effector molecule. However, use of the Tet-On system has been fraught with difficulties, including high background expression in the absence of effector molecules and inconsistent gene induction. Recently, secondgeneration Tet-On transactivators (TAs) have been described. In HeLa cells, they are far more efficient than the original reverse TA protein, and they exhibit lower background activity in the absence of effectors. Here we examine the most promising TA in transgenic Drosophila and characterize its in vivo properties. We report that low levels of doxycycline, when added to normal fly food, efficiently and rapidly induce target transgenes in adults, larvae, and embryos. This TA is superior to all other Tet-On proteins, and its performance is comparable to that of the widely used Tet-Off TA. In addition, combining the improved Tet-On TA with the Gal4-UAS (upstream-activating sequence) system produces robust, spatially restricted, temporally controlled transgene induction. Because this Tet-On TA is significantly more efficient than previous ones used in Drosophila, it is also possible to modulate gene induction by controlling the dosage of the antibiotic in the food.

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“…Previous studies of two other MADF-containing Drosophila proteins also describe the need for tight gene regulation. nalyot, a hypomorphic allele of adf1, disrupts olfactory memory in adults (DeZazzo et al, 2000). A null mutation of this gene causes larval lethality.…”

Section: Essential Functions Of Mes2mentioning

confidence: 99%

Mes2, a MADF‐containing transcription factor essential for Drosophila development

Zimmermann

Furlong

Suyama

et al. 2006

Developmental Dynamics

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The development of the Drosophila mesoderm is initiated by the basic helix-loop-helix transcription factor twist. We identified a gene encoding a putative transcription factor, mes2, in a screen for essential mesoderm-expressed genes that function downstream of twist. Mes2 protein belongs to a family of 48 Drosophila proteins containing MADF domains. MADF domains exist in worms, flies, and fish. Mes2 is a nuclear protein first produced in trunk and head mesoderm during late gastrulation. At later embryonic stages, mes2 is expressed in glia of the central and peripheral nervous systems, and in tissues derived from the head mesoderm. We have identified a null mutation of mes2 that leads to developmental arrest in first instar larvae. Increased production of Mes2 in multiple embryonic and larval tissues almost always causes lethality. The ubiquitous or epidermal misexpression of mes2 in the embryo causes a dramatic loss of epidermal integrity resulting in the failure of dorsal closure. Our data show that the precise regulation of mes2 expression is critical for normal development in Drosophila and implicate Mes2 in the regulation of essential target genes. Developmental Dynamics 235:3387-3395, 2006.

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nalyot, a Mutation of the Drosophila Myb-Related Adf1 Transcription Factor, Disrupts Synapse Formation and Olfactory Memory

Cited by 70 publications

References 43 publications

A Drosophila model for Angelman syndrome

A Drosophila model for Angelman syndrome

Tetracycline-inducible systems for Drosophila

Mes2, a MADF‐containing transcription factor essential for Drosophila development

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