Open Close
General Information
Symbol
Dmel\brat11
Species
D. melanogaster
Name
FlyBase ID
FBal0001236
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
point mutation
Nucleotide change:

C19170480T

Amino acid change:

Q779term | brat-PA; Q779term | brat-PB; Q779term | brat-PC; Q779term | brat-PE; Q779term | brat-PF

Reported amino acid change:

Q779term

Comment:

Site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.

Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Cytology
Nature of the lesion
Statement
Reference

Amino acid replacement: Q779term.

Expression Data
Reporter Expression
Additional Information
Statement
Reference
 
Marker for
Reflects expression of
Reporter construct used in assay
Human Disease Associations
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 1 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
model of  brain cancer
is ameliorated by prosUAS.cMa
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

bratDG19310/brat11 mutant clones originating from either a single ase+ immature intermediate neural progenitor (INP) or INP contain a similar number of neuroblasts (reverted clones) as controls.

brat11/brat2L-192-9 larvae show an increase in total bouton number and in number of satellite boutons at the neuromuscular junction compared to wild type. Ultrastructurally, the presynaptic mitochondria and postsynaptic subsynaptic reticulum appear largely normal in the mutant boutons. However, vesicle density within the bouton is moderately, but significantly, reduced and a subpopulation of vesicles are larger than in wild type. There are fewer synaptic vesicles within a 200nm radius of the T-bar than normal, and the mean synaptic vesicle diameter within the active zone is significantly increased. There is a significant increase in the number of presynaptic membrane ruffles within the active zone and the mean length of the postsynaptic density is increased.

The mean EJP amplitude and mEJP frequency is not significantly different from wild type at the neuromuscular junction of brat11/brat2L-192-9 larvae. However, mean mEJP amplitude is increased compared to wild type and quantal content is significantly reduced.

The neuromuscular junctions of brat11/brat2L-192-9 larvae show reduced uptake of FM1-43 dye compared to wild type, indicating a defect in endocytosis.

brat11/bratDG19310 larval brains contain supernumerary type II neuroblasts.

brat11/bratk06028 larval brains contain supernumerary type II neuroblasts.

brat11 germ line clones dispay an increased growth phenotype, with larger cells than wild-type. There is an increase in the number of germline stem cells in these mutants.

In late third instar brat11 mutant larvae, brain hemispheres are markedly enlarged and characterized by cellular overgrowth whereas ventral ganglia appear normal. The central brain is characterized by dense cellular masses of numerous small and pleiomorphic cells in addition to a limited number of large cells. At earlier larval stages, brain hemispheres, brat11 mutants brain hemispheres are the same overall size as wild-type larvae.

brat11 clones in the central brain of third instar larvae populate large areas of the brain hemispheres and are up to ten times larger than wild-type central brain clones: over 80% of the mutant clones comprise 200-1000 cells, while wild-type clones comprise >100 cells. In the early larval instar, brat11 clones are clearly distinguishable and separated from one another, but by the late third instar almost all of the central brain appears to be covered by an indistinguishable clonal cell mass. Cells in brat11 clones lack axonal processes. In the ventral ganglia, brat11 clones are recovered at a similar frequency to wild-type clones.

brat11 clones induced in first instar larvae appear dramatically enlarged in size and cell number in the adult brain and appear to be mitotically active (according to phosphorylated His3 staining).

In brat11 homozygous mutant larvae there is a dramatic increase in neuroblast number, over 500 by 96 hours after larval hatching and an estimated several thousand by 120 hours after larval hatching. This corresponds to a reduction in elav staining, indicating ectopic neuroblast generation at the expense of neurons.

brat11 neuroblasts generate GMC-sized progeny that are cell cycle delayed and continue to express neuroblast markers; some of these 'GMCs' differentiate into neurons, but many appear to develop into proliferative neuroblasts.

brat11 homozygous somatic clones in third instar larvae are consistently larger than wild-type. the cells themselves are larger than individual wild-type cells. Mutant cells also have nucleoli that are 18 to 33% larger than wild-type cells, mutant dells contain 1.6 times more rRNA than control cells.

The median survival of adult hosts transplanted with brat11/brat14 brain fragments is reduced compared to adult hosts transplanted with wild-type brain fragments. Cells from transplanted brat11/brat14 brain fragments form at least one secondary tumour in the wild-type host in 84% of cases. Imaginal discs from brat11/brat14 larvae form secondary tumours in 53% of hosts.

Hemizygous larval brain tissue transplanted into the abdomens of adult female hosts shows unrestrained and invasive growth.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement
Reference

bratDG19310/brat11 has abnormal neuroanatomy phenotype, enhanceable by erm[+]/erm1

bratDG19310/brat11 has abnormal neuroanatomy phenotype, enhanceable by brm[+]/brm2

bratDG19310/brat11 has abnormal neuroanatomy phenotype, enhanceable by mor[+]/mor1

NOT Enhanced by
Suppressed by
NOT suppressed by
Other
Phenotype Manifest In
Enhanced by
Statement
Reference
NOT Enhanced by
Suppressed by
NOT suppressed by
Other
Additional Comments
Genetic Interactions
Statement
Reference

One copy of erm1 enhances the supernumerary type II neuroblast phenotype seen in bratDG19310/brat11 mutants.

In contrast to bratDG19310/brat11 clones alone, clones originating from either a single ase+ immature Intermediate Neural Progenitor (INP) or INP that are also heterozygous for erm1 contain an increased number of neuroblasts 'reverted clones'. This phenotype is reversed upon expression of ermScer\UAS.T:Ivir\HA1 under the control of Scer\GAL4GMR9D11. This rescue is seen using an insertion line of the driver that expressed in ase[-] INPs (P{GMR9D11-GAL4}2) and one that expresses in ase[+] INPs (P{GMR9D11-GAL4}attP2).

Expression of ermScer\UAS.T:Ivir\HA1 under the control of an insertion of Scer\GAL4GMR9D11 that expresses in ase[-] immature Intermediate Neural Progenitors (INPs) (P{GMR9D11-GAL4}2) suppresses the supernumerary neuroblast phenotype seen in bratDG19310/brat11 mutant larval brains. Expression of ermScer\UAS.T:Ivir\HA1 using a line that expresses in ase[+] INPs (P{GMR9D11-GAL4}attP2) does not suppress the phenotype.

Expression of kluScer\UAS.T:Ivir\HA1 under the control of an insertion of Scer\GAL4GMR9D11 that expresses in ase[-] immature Intermediate Neural Progenitors (INPs) (P{GMR9D11-GAL4}2) enhances the supernumerary neuroblast phenotype seen in bratDG19310/brat11 mutant larval brains. No enhancement is seen when kluScer\UAS.T:Ivir\HA1 is expressed using an insertion of Scer\GAL4GMR9D11 that expresses in ase[+] INPs (P{GMR9D11-GAL4}attP2).

Expression of dpnScer\UAS.cWa under the control of an insertion of Scer\GAL4GMR9D11 that expresses in ase[-] immature Intermediate Neural Progenitors (INPs) (P{GMR9D11-GAL4}2) enhances the supernumerary neuroblast phenotype seen in bratDG19310/brat11 mutant larval brains. A milder enhancement is seen when dpnScer\UAS.cWa is expressed using an insertion of Scer\GAL4GMR9D11 that expresses in ase[+] INPs (P{GMR9D11-GAL4}attP2).

Expression of E(spl)mγ-HLHScer\UAS.cLa under the control of an insertion of Scer\GAL4GMR9D11 that expresses in ase[-] immature Intermediate Neural Progenitors (INPs) (P{GMR9D11-GAL4}2) strongly enhances the supernumerary neuroblast phenotype seen in bratDG19310/brat11 mutant larval brains. A milder enhancement is seen when E(spl)mγ-HLHScer\UAS.cLa is expressed using an insertion of Scer\GAL4GMR9D11 that expresses in ase[+] INPs (P{GMR9D11-GAL4}attP2).

One copy of osa308 enhances the supernumerary neuroblast phenotype seen in bratDG19310/brat11 mutants.

One copy of brm2 enhances the supernumerary neuroblast phenotype seen in bratDG19310/brat11 mutants.

One copy of mor1 enhances the supernumerary neuroblast phenotype seen in bratDG19310/brat11 mutants.

Expression of brmK804R.Scer\UAS.T:Ivir\HA1 under the control of an insertion of Scer\GAL4GMR9D11 that expresses in ase[-] immature Intermediate Neural Progenitors (INPs) (P{GMR9D11-GAL4}2) enhances the supernumerary neuroblast phenotype seen in bratDG19310/brat11 mutant larval brains. Expression of brmK804R.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4wor.PA also enhances the phenotype. No enhancement is seen when brmK804R.Scer\UAS.T:Ivir\HA1 is expressed using an insertion of Scer\GAL4GMR9D11 that expresses in ase[+] INPs (P{GMR9D11-GAL4}attP2).

Expression of armS10.Scer\UAS.T:Hsap\MYC in type II neuroblasts or ase- immature intermediate neural progenitors (INPs) enhances the supernumerary neuroblast phenotype seen in bratDG19310/brat11 larval brains, whereas expression in ase+ immature INPs does not (different insertions of Scer\GAL4GMR9D11 are used to drive expression in each case).

Expression of panΔN.Scer\UAS in type II neuroblasts or ase- immature intermediate neural progenitors (INPs) suppresses the supernumerary neuroblast phenotype seen in bratDG19310/brat11 larval brains, whereas expression in ase+ immature INPs does not (different insertions of Scer\GAL4GMR9D11 are used to drive expression in each case).

The neuromuscular junction overgrowth phenotype (increased total number of boutons and increased number of satellite boutons) of brat11/brat2L-192-9 larvae is not suppressed by either witA12/+ or tkv7/+.

The neuromuscular junction overgrowth phenotype (increased total number of boutons and increased number of satellite boutons) of brat11/brat2L-192-9 larvae is significantly suppressed by Mad12/+ and by Df(2L)BSC162/+.

The reduced uptake of FM1-43 dye seen at the neuromuscular junction in brat11/brat2L-192-9 larvae is significantly suppressed by Mad12/+ and by Df(2L)BSC162/+.

kluunspecified/+ strongly suppresses the formation of supernumerary type II neuroblasts which is seen in brat11/bratDG19310 larval brains.

The formation of supernumerary type II neuroblasts is suppressed in homozygous kluunspecified type II neuroblast clones in brat11/bratk06028 larval brains.

Expression of prosScer\UAS.cMa, under the control of Scer\GAL4αTub84B.PL, in brat11 mutant larval clones significantly suppresses the overproliferation phenotype in these clones in the central larval brain. Over 90% of Scer\GAL4αTub84B.PL>prosScer\UAS.cMa, brat11 clones in the central brain have <100 cells, while over 80% of brat11 clones have 200-1000 cells.

Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Comments

Expression of either bratScer\UAS.T:Hsap\MYC, bratΔB-box-1.Scer\UAS.T:Hsap\MYC, bratΔB-box-2.Scer\UAS.T:Hsap\MYC, bratΔC-coil.Scer\UAS.T:Hsap\MYC or bratΔNHL.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4wor.PA suppresses the supernumerary type II neuroblast phenotype seen in brat11/Df(2L)Exel8040 larval brains.

Expression of bratΔB-boxes.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4wor.PA fails to suppress the supernumerary type II neuroblast phenotype seen in brat11/Df(2L)Exel8040 larval brains.

Expression of bratScer\UAS.T:Zzzz\FLAG under the control of either Scer\GAL4elav.PU or Scer\GAL4RapGAP1-OK6 at 18[o]C partially rescues the increase in number of satellite boutons at the neuromuscular junction (NMJ) seen in brat11/brat2L-192-9 larvae. Expression under the control of Scer\GAL4Mhc.PW at 18[o]C does not rescue the NMJ phenotype.

Expression of bratScer\UAS.T:Zzzz\FLAG under the control of Scer\GAL4elav.PU at 18[o]C partially rescues the endocytotic defects seen at the NMJ of brat11/brat2L-192-9 larvae.

Expression of bratScer\UAS.cSa under the control of Scer\GAL4αTub84B.PL in brat11 mutant clones partially rescues the overproliferation phenotype in the central larval brain.

Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer

Wright.

External Crossreferences and Linkouts ( 3 )
Crossreferences
GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
Synonyms and Secondary IDs (3)
References (23)