Evidence map›Paper›PMID 27762066›Full record

ArticleGenes, brain, and behavior2017

A new brain dopamine-deficient Drosophila and its pharmacological and genetic rescue.

K Cichewicz, E J Garren, C Adiele, Y Aso, Z Wang, M Wu, S Birman, G M Rubin, J Hirsh

Open access · bronzeAbstract read
In one paragraph

Article in Genes, brain, and behavior, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 58 citations in OpenAlex.

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  7. Non-uniform chromosomal SNP density biases sites of meiotic crossovers inbioRxiv : the preprint server for biology · 2025
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  8. Hippo signaling regulates cuticle pigmentation and dopamine metabolism inbioRxiv : the preprint server for biology · 2025
    Article
  9. RNAi-based screen for pigmentation inbioRxiv : the preprint server for biology · 2025
    Article
  10. Article
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  14. ACS chemical neuroscience · 2023
    Article
  15. Article
  16. The Use ofBiomedicines · 2022
    Review
  17. Article
  18. A pair of dopamine neurons mediate chronic stress signals to induce learning deficit inProceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

K CichewiczDepartment of Biology, University of Virginia, Charlottesville.ORCID 0000-0001-5926-3663
E J GarrenDepartment of Biology, University of Virginia, Charlottesville.
C AdieleDepartment of Biology, University of Virginia, Charlottesville.
Y AsoJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
Z WangDepartment of Biology, University of Virginia, Charlottesville.
M WuDepartment of Biology, University of Virginia, Charlottesville.
S BirmanGenes, Circuits, Rhythms and Neuropathology, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, Paris, France.
G M RubinJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.
J HirshDepartment of Biology, University of Virginia, Charlottesville.
University of Virginia · USHoward Hughes Medical Institute · USCentre National de la Recherche Scientifique · FR

Funding

Mechanisms of compensation for loss of brain dopamineR01GM084128 · NIGMS · UNIVERSITY OF VIRGINIA · PI HIRSH, JAY · 2009 to 2023
$3.8M
NIGMS NIH HHS R01 GM084128
6 · The paper itself

Abstract

Dopamine (DA) is a neurotransmitter with conserved behavioral roles between invertebrate and vertebrate animals. In addition to its neural functions, in insects DA is a critical substrate for cuticle pigmentation and hardening. Drosophila tyrosine hydroxylase (DTH) is the rate limiting enzyme for DA biosynthesis. Viable brain DA-deficient flies were previously generated using tissue-selective GAL4-UAS binary expression rescue of a DTH null mutation and these flies show specific behavioral impairments. To circumvent the limitations of rescue via binary expression, here we achieve rescue utilizing genomically integrated mutant DTH. As expected, our DA-deficient flies have no detectable DTH or DA in the brain, and show reduced locomotor activity. This deficit can be rescued by l-DOPA/carbidopa feeding, similar to human Parkinson's disease treatment. Genetic rescue via GAL4/UAS-DTH was also successful, although this required the generation of a new UAS-DTH1 transgene devoid of most untranslated regions, as existing UAS-DTH transgenes express in the brain without a Gal4 driver via endogenous regulatory elements. A surprising finding of our newly constructed UAS-DTH1m is that it expresses DTH at an undetectable level when regulated by dopaminergic GAL4 drivers even when fully rescuing DA, indicating that DTH immunostaining is not necessarily a valid marker for DA expression. This finding necessitated optimizing DA immunohistochemistry, showing details of DA innervation to the mushroom body and the central complex. When DA rescue is limited to specific DA neurons, DA does not diffuse beyond the DTH-expressing terminals, such that DA signaling can be limited to very specific brain regions.

Indexed as

AnimalsBrainDisease Models, AnimalDopamineDopaminergic NeuronsDrosophilaLevodopaMaleNeurotransmitter AgentsTyrosine 3-MonooxygenaseDopamineLevodopaNeurotransmitter AgentsTyrosine 3-MonooxygenaseCarbiodopacentral complexDopamine deficiencydopamine rescueDrosophilaDrosophila behaviorgenetic model of Parkinson's diseasel-DOPAmushroom bodyParkinson's disease

Identifiers

PMID27762066
PMCPMC5492937
OpenAlexW2533524158

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.