General Information
Symbol
Dmel\hiwND8
Species
D. melanogaster
Name
FlyBase ID
FBal0118196
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
ND8
Mutagen
    Nature of the Allele
    Mutagen
    Mutations Mapped to the Genome
     
    Type
    Location
    Additional Notes
    References
    point mutation
    Nucleotide change:
    G15054603A
    Amino acid change:
    W1930term | hiw-PA; W1930term | hiw-PB
    Reported amino acid change:
    Y1930term
    Comment:
    G to A nucleotide change at the second or third position of the wild type Trp codon leads to a nonsense mutation (exact site of mutation unspecified). The mutation was annotated at the second base of the codon.
    Associated Sequence Data
    DNA sequence
    Protein sequence
     
     
    Progenitor genotype
    Cytology
    Nature of the lesion
    Statement
    Reference
    Amino acid replacement: Y1930term.
    Expression Data
    Reporter Expression
    Additional Information
    Statement
    Reference
     
    Marker for
    Reflects expression of
    Reporter construct used in assay
    Human Disease Model Data
    Disease Ontology
    Models ( 0 )
    Disease
    Evidence
    References
    Interactions ( 0 )
    Disease
    Interaction
    References
    Comments ( 0 )
     
    Phenotypic Data
    Phenotypic Class
    Phenotype Manifest In
    Detailed Description
    Statement
    Reference
    Mutant larvae show an increase in both branch and bouton number at the neuromuscular junction compared to controls.
    Expression of hiwΔPHR.Scer\UAS.T:Zzzz\TAP presynaptically in hiwND8 heterozygotes, under the control of Scer\GAL4elav.Switch.PO results in mild synaptic terminal overgrowth. Expression of hiwΔRCC1.Scer\UAS.T:Zzzz\TAP presynaptically in hiwND8 heterozygotes, under the control of Scer\GAL4elav.Switch.PO results in moderate synaptic terminal overgrowth. Expression of hiwHindIII.Scer\UAS.T:Zzzz\His6,T:Hsap\MYC presynaptically in hiwND8 heterozygotes, under the control of Scer\GAL4elav.Switch.PO results in moderate synaptic terminal overgrowth. Expression of hiwΔN.Scer\UAS.T:Zzzz\TAP presynaptically in hiwND8 heterozygotes, under the control of Scer\GAL4elav.Switch.PO results in notable synaptic terminal overgrowth.
    hiwND8 mutants exhibit defects in the giant fiber-tergotrochanteral motorneuron synapse, such as ectopic axonal branches from the presynaptic terminal.
    hiwND8 mutants exhibit dramatic synaptic overgrowth at the neuromuscular junction of muscle 4: a 4-fold increase in the number of boutons and synaptic branches, and a 2-fold increase in total synaptic area. The hiwND8 mutant phenotype also causes a 66% reduction in bouton size and a 70% reduction in the average intensity and a 50% reduction in total intensity of staining for synaptic vesicle proteins. hiwND8 mutants show both reduced quantal size (response to a single vesicle) and reduced quantal content (number of vesicles released by the nerve).
    Morphological analysis at the neuromuscular junction of hiwND8 mutants reveals a dramatic synaptic overgrowth phenotype apparent at every type I synapse. Using the MN4-Ib motoneuron as a model, hiwND8 mutants exhibit a fivefold increase in the numbers of both synaptic bouton and branch points when compared with wild-type neuromuscular junctions. The synaptic span also increases from approximately 15% in wild-type to approximately 40%. Although there is an increase in the number of synaptic boutons, there is an approximate 70% decrease in the average bouton size compared to wild-type.
    Eye size is similar to controls in mutant flies.
    The pattern of motor innervation of muscles 12 and 13 is also correct in hiwunspecified mutants, although the terminal branches are much longer and more numerous.
    External Data
    Interactions
    Show genetic interaction network for Enhancers & Suppressors
    Phenotypic Class
    Phenotype Manifest In
    Suppressed by
    Statement
    Reference
    hiwND8 has NMJ bouton | larval stage phenotype, suppressible by p38a1
    hiwND8 has neuromuscular junction phenotype, suppressible | partially by wnd[+]/wnd1
    hiwND8 has bouton phenotype, suppressible | partially by wnd[+]/wnd1
    hiwND8 has bouton phenotype, suppressible by wnd1/wnd2
    NOT suppressed by
    Suppressor of
    Statement
    Reference
    Additional Comments
    Genetic Interactions
    Statement
    Reference
    hiwND8;Trpml1 double mutant larvae do not show the increase in number of neuromuscular junction boutons characteristic for the hiwND8 single mutants. Ectopic expression of RagA-BT16N.Scer\UAS under the control of the Scer\GAL4VGlut-OK371 driver in hiwND8 mutant larvae background rescues the increased number of neuromuscular junction boutons phenotype characteristic for hiwND8 mutants. Ectopic expression of raptorJF01088 under the control of the Scer\GAL4VGlut-OK371 driver in hiwND8 mutant larvae background partially rescues the increased number of neuromuscular junction boutons phenotype characteristic for hiwND8 mutants. Expression of cln3HMS01476 RNAi under the control of the Scer\GAL4VGlut-OK371 in the hiwND8 mutant background lowers the increased number of neuromuscular junction boutons characteristic for the hiwND8 mutant third instar larvae.
    p38bKG01337/Df(2L)b80e3 suppresses the increase in branch and bouton number at the neuromuscular junction which is seen in hiwND8 larvae. hiwND8 suppresses the increase in maximum bouton diameter which is seen at the neuromuscular junction in p38bKG01337/Df(2L)b80e3 larvae. Mpk21 suppresses the increase in branch and bouton number at the neuromuscular junction which is seen in hiwND8 larvae.
    Simultaneous expression of p38bDN.Scer\UAS (under the control of Scer\GAL4BG380) and Mpk21 does not suppress the hiwND8 synaptic phenotype. Expression of bskK53R.Scer\UAS (under the control of Scer\GAL4BG380) suppresses the hiwND8 synaptic phenotype, reducing the number of synaptic boutons and branches and increasing bouton size and the intensity of synaptic vesicle markers. Removing one copy of wnd1 suppresses the hiwND8 neuromuscular junction of muscle 4 phenotype by approximately 50%. hiwND8; wnd1/wnd2 mutants are not significantly different from wild-type, indicating complete suppression of hiwND8. wnd1/wnd2 mutants do not suppress the hiwND8 defect in quantal size: both the amplitude and the frequency of spontaneous miniature events in the hiwND8; wnd1/wnd2 double mutant are similar to wild-type. In contrast, the evoked potentials of the double mutant are only modestly increased, and this is due entirely to the increased quantal size. The quantal content, calculated as the excitatory junction potential (EJP) amplitude divided by the miniature EJP (mEJP) remains the same between hiwND8 and hiwND8; wnd1/wnd2 double mutants. Therefore wnd does not suppress the primary defect in hiwND8 synaptic function, the reduced number of vesicles released by the nerve. Expression of kayFbz.Scer\UAS, under the control of Scer\GAL4BG380, confers dramatic suppression of the hiwND8 synaptic phenotype, reducing bouton number and branching (42%) and increasing the intensity of staining for synaptic vesicle markers at the synapse. Expression of JraJbz.Scer\UAS, under the control of Scer\GAL4BG380 does not suppress the hiwND8 synaptic phenotype.
    The small eye phenotype caused by co-expression of gigScer\UAS.cTa and Tsc1Scer\UAS.cTa under the control of Scer\GAL4ey.PH is enhanced by hiwND8.
    Xenogenetic Interactions
    Statement
    Reference
    Complementation and Rescue Data
    Comments
    Presynaptic expression of hiwScer\UAS.fl (under the control of Scer\GAL4elav.PLu) resuces the deficit in both spontaneous and evoked neurotransmitter release in hiwND8 hemizygotes. The quantal content, which is estimated by the mean mEJP amplitude, is also rescued. Expresion of hiwScer\UAS.fl postsynaptically, under the control of Scer\GAL4G7 fails to rescue the hiwND8 synaptic overgrowth phenotype. Expression of hiwScer\UAS.T:Avic\GFP-EGFP throughout development, under the control of Scer\GAL4elav.Switch.PO, results in a robust rescue of the hiwND8/Y morphological phenotype with an approximate 77% reduction in the number of boutons, along with robust rescue of quantal content. In the absence of RU486, which activates transcription of Scer\GAL4elav.Switch.PO, and therefore hiwScer\UAS.T:Avic\GFP-EGFP, hiwND8/Y synapses are still extremely overgrown; however, there is apparently some leaky expression because there is a 27% decrease in the number of synaptic boutons. Leaky expression leads to a nearly complete rescue of the quantal content, indicating that very low dose of hiw are effective in rescuing synaptic function. When RU486 is added during larval development, there is an additional approximately 25% reduction in bouton number, compared with hiwND8/Y larvae in the absence of RU486. Compared with leaky expression, late expression of hiwScer\UAS.T:Avic\GFP-EGFP does not lead to a significant decrease in synaptic branching or synaptic expansion in hiwND8/Y mutants. There is a complete rescue of synaptic function, with a significant increase in quantal content compared to leaky hiwScer\UAS.T:Avic\GFP-EGFP expression in the absence of RU486.
    Images (0)
    Mutant
    Wild-type
    Stocks (1)
    Notes on Origin
    Discoverer
    External Crossreferences and Linkouts ( 0 )
    Synonyms and Secondary IDs (3)
    References (11)