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General Information
Name
anxiety modulators, fly wall-following model
FlyBase ID
FBhh0001005
Disease Ontology Term
Parent Disease
OMIM
Overview

Using flies, a wall-following (WAFO) assay has been developed to quantify response to anxiety-inducing or anxiety-reducing stimuli or pharmaceuticals. In an enclosed area, Drosophila typically stay close to the walls during spontaneous locomotion, crossing the center of the field infrequently. A reduction in the WAFO score (increased travel away from the walls) is interpreted as a reduction in anxiety, and an increase in WAFO as an increase in anxiety. The assay must be performed on multiple individual flies, since there is a significant amount of variation between individuals under the same conditions.

This model has been supported by experiments using known modulators of anxiety: (1) WAFO is reduced when the flies are fed diazepam (Valium), which acts via the inhibitory neurotransmitter GABA; (2) WAFO is increased in animals carrying loss-of-function mutations in 5-HT1B (serotonin class 1 receptor) or SerT (serotonin transporter, ortholog of human SLC6A4, see OMIM:607834) and is decreased when either gene is overexpressed; (3) WAFO is increased under environmental stress such as heat shock; (4) WAFO is increased under conditions of prolonged social isolation; (5) supporting observations made in a mouse system, WAFO is reduced by loss-of-function mutations in Dh44-R1 (orthologous to CRHR2 and CRHR1, corticotropin releasing hormone receptors); (6) the large increase in WAFO induced by heat shock is ameliorated by diazepam.

The human Hsap\SLC6A4 and Hsap\HTR1D genes have been introduced into flies, but have not been used in the context of this model.

This wall-following assay has been used to assess new gene candidates postulated to affect anxiety-related behaviors; see human disease model reports 'anxiety modulator(s), serotonin class 2 receptor(s)' (FBhh0001006), 'anxiety modulator(s), genes affecting actin filament stability' (FBhh0001007), and 'anxiety modulator(s), CCK-like receptors' (FBhh0001008).

[updated Apr. 2019 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: anxiety modulators, fly wall-following model
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information
External links
Disease synonyms
anxiety modulators, WAFO assay
Ortholog Information
Human gene(s) in FlyBase
    Other mammalian ortholog(s) used
      D. melanogaster Gene Information (3)
      Gene Snapshot
      5-hydroxytryptamine (serotonin) receptor 1B (5-HT1B) encodes a 5-hydroxytryptamine (serotonin) GPCR that belongs to the Class A GPCR family. They bind and transmit the signal from the neurotransmitter 5-HT (serotonin). The family can be subdivided into several subclasses based on pharmacology, signal transduction and structure. There are 5 genes encoding serotonin receptors in the Drosophila melanogaster genome: 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B, and 5-HT7. [Date last reviewed: 2019-09-26]
      Gene Groups / Pathways
      Comments on ortholog(s)
      Moderate-scoring ortholog of human HTR1A, HTR1B, HTR1D, and HTR1F; additional related genes in both species). Dmel\5-HT1B shares 28-31% identity and 42-45% similarity with the listed human genes.
      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      In progress.Contributions welcome.
      Gene Groups / Pathways
      Comments on ortholog(s)
      High-scoring ortholog of human SLC6A4 (1 Drosophila to 1 human; additional related genes in both species). Dmel\SerT shares 55% identity and 71% similarity with the human gene.
      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Gene Snapshot
      Diuretic hormone 44 receptor 1 (Dh44-R1) encodes a G-Protein Coupled Receptor of the Family B class of GPCRs (Secretin Receptor-like). It is involved in regulation of diuresis, sperm storage in females and circadian control of locomotion. [Date last reviewed: 2018-10-18]
      Gene Groups / Pathways
      Comments on ortholog(s)
      High-scoring ortholog of human CRHR2, moderate-scoring ortholog of CRHR1 (2 Drosophila to 2 human). Dmel\Dh44-R1 shares 35-36% identity and 51-53% similarity with the human genes.
      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Synthetic Gene(s) Used (0)
      Summary of Physical Interactions (1 groups)
      protein-protein
      Interacting group
      Assay
      References
      phenotype-based detection assay, inferred by author
      Alleles Reported to Model Human Disease (Disease Ontology) (4 alleles)
      Models Based on Experimental Evidence ( 2 )
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Models Based on Experimental Evidence ( 2 )
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Genetic Tools, Stocks and Reagents
      Sources of Stocks
      Contact lab of origin for a reagent not available from a public stock center.
      Bloomington Stock Center Disease Page
      Selected mammalian transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      amorphic allele - molecular evidence
      CRISPR/Cas9
      amorphic allele - molecular evidence
      gene targeting by homologous recombination
      amorphic allele - molecular evidence
      minos activity
      References (3)