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General Information
Symbol
Dmel\Pten117
Species
D. melanogaster
Name
FlyBase ID
FBal0120658
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
PTEN2L117, dPTEN117
Key Links
Mutagen
    Nature of the Allele
    Mutagen
    Mutations Mapped to the Genome
     
    Type
    Location
    Additional Notes
    References
    Associated Sequence Data
    DNA sequence
    Protein sequence
     
     
    Progenitor genotype
    Cytology
    Nature of the lesion
    Statement
    Reference

    5bp deletion producing a frameshift at amino acid position 165 resulting in the insertion of 35 new codons (AYKGPKRCDNPISASICSVFFQTSLFKCSIFESKP) before the new stop codon located in the catalytic domain.

    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 ( 0 )
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 0 )
    Disease
    Interaction
    References
    Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
     
    Disease-implicated variant(s)
     
    Phenotypic Data
    Phenotypic Class
    Phenotype Manifest In
    Detailed Description
    Statement
    Reference

    Pten117 mutant adult wings are slightly more elongated along the proximal-distal axis the wild-type ones.

    Pten117/Pten2L100 mutant larvae and adult flies are larger than wild-type controls under normal food conditions. The prospective adult tissues, the eye and wing imaginal discs are larger than in controls. These larvae are highly sensitive to a reduction in yeast content, and although still larger, they do not survive to pupariation when reared on 10g/l yeast food. Pten117/Pten2L100 mutant larvae reared on 100g/l yeast food at 39% larger than controls reared on 100g\l yeast food.

    Pten117 imaginal disc clones are enlarged in larvae fed with yeasted food but do not severely impact on the structure of the imaginal discs and of the adult eyes. Under mild starvation conditions (30g/l yeast), Pten117 mutant clones are further increased in size, resulting in an overall increase in disc size as compared to discs harboring control clones. Reducing the yeast concentration to 20g/l and below leads to a massive size increase in the Pten117 clones and to a concomitant reduction of the surrounding tissue. Furthermore, the Pten117 clones fuse and render the discs a lobed appearance. At 5g/l yeast concentration, the eye discs with Pten117 mutant tissue are severely overgrown with polyp-like structures protruding from the discs. The resulting adult eyes display strong malformations and outgrowths, indicating a loss of epithelial integrity. In some cases, no clones can be recovered in the adult eyes, probably due to a collapse of the Pten117 clones resulting in melanized scars. Tangential eye sections do not reveal any structural defects in ommatidial arrangement. Pten117 mutant cells overgrow in a cell-autonomous manner as the enlarged ommatidia are exclusively composed of mutant cells. The overgrowth phenotype of Pten117 clones is not specific to the eye; it is observed in other imaginal tissues like the wing disc. As the Pten117 clones are overgrown after only 36hrs post induction, developmental delay is not the cause of the overgrowth.

    Pten117 mutant eye clones exhibit overgrowth. The entire eye is enlarged in flies raised on normal food. Under starvation conditions, the mutant tissue occupies most of the adult eye and the wild-type tissue is severely reduced. This over-representation of the mutant tissue results in an absolute increase of eye size under starvation as compared to normal food conditions. In eyes almost entirely composed of Pten117 mutant tissue, the eye size increase is mainly caused by larger ommatidia (+27%), and to a minor extent by more ommatidia (+14%). Under starvation conditions (10g/l yeast), the ommatidial size is roughly proportionally reduced in wild-type and Pten117 mutant eyes. While the ommatidia number is decreased by 6% in wild-type eyes, it is massively decreased in Pten117 mutant eyes (+44%). Since the composition of the Pten117 mutant ommatidia remains unchanged, the size and number of ommatidia reflects cell size and cell number, indicating a switch from hypertrophy to hyperplasia.

    Whereas only a few apoptotic cells are detected in heterozygous Pten117 cells under both fed and starving conditions, increased levels of apoptosis are observed within overgrowing Pten117 clones.

    When transferred from starvation (10g/l yeast) to normal food (100g/l yeast) within the first 72 hours, Pten117 imaginal disc clones, the overgrowth of the mutant clones is efficiently rescued. Later shifts are no longer effective in suppressing the overgrowth. It is sufficient to transfer larvae within the first 48 hours from normal to starvation food to produce the overgrowth phenotype. After this time point, Pten117 imaginal disc clones do not acquire the full growth advantage over the surrounding tissue.

    Under severe starvation (5g/l yeast content), the Pten117 mutant polyp-like structures outgrowing from the eye discs exhibit very high levels of apoptosis. Scars are visible, in the corresponding adult eyes, left behind by the collapsing clones. These eyes contain more wild-type cells, indicating that the lost Pten117 mutant tissue is compensated for.

    A decrease in shoulder area (as a measure for body size) is observed under starvation but not under control conditions in fly heads mostly composed of Pten117 mutant clones. Consistently, the wing size and the fat body nuclear size are reduced, especially in animals raised under starvation conditions. Thus, the growth-reducing non-autonomous effect of Pten mutant tissue acts systemically.

    Pten117 mutant glial clones do not overgrow, but do show aberrant cytoplasmic projections.

    Pten117 mutant optic lobe clones in adult flies contain a modest number of excess and abnormal glia relative to wild type controls.

    Head capsule enlarged - bighead phenotype.

    Pten2L100/Pten117 larvae, pupae and adults are substantially increased in size compared to control larvae. Mosaic flies in which the head is composed of homozygous Pten117 cells (clones generated using the "eyFLP" system) have disproportionally large heads. Pten2L100/Pten117 adults are hypersensitive to starvation conditions compared to wild type.

    Somatic clones of Pten117 in the developing eye cause strong overgrowth of the eye. The size of ommatidia in clones is increased relative to wild-type.

    Generation of flies in which the eye imaginal disc is homozygous for Pten117 (using the "ey-Flp" system) results in an increase in eye and head size compared to wild type. The increase in eye size is due to an increase in cell number and cell size as indicated by an increase in number and size of ommatidia.

    Loss of Pten function in the eye and head capsule results in a fly with a big head.

    External Data
    Interactions
    Show genetic interaction network for Enhancers & Suppressors
    Phenotypic Class
    Enhanced by
    Statement
    Reference
    NOT Enhanced by
    Suppressed by
    Statement
    Reference

    Pten117 has increased cell death | somatic clone | nutrition conditional phenotype, suppressible by bskDN.UAS/Scer\GAL4Act5C.PP

    Pten117 has increased cell growth | somatic clone | nutrition conditional phenotype, suppressible by bskDN.UAS/Scer\GAL4Act5C.PP

    Pten117 has increased cell growth | nutrition conditional phenotype, suppressible by Akt1

    Pten117 has increased cell growth phenotype, suppressible by Akt1

    Pten117 has increased cell growth | nutrition conditional phenotype, suppressible by Akt3

    Pten117 has increased cell growth phenotype, suppressible by Akt3

    Pten117 has increased cell growth | nutrition conditional phenotype, suppressible by gigUAS.cTa/Tsc1UAS.cTa/Scer\GAL4GMR.PU

    Pten117 has increased cell growth | somatic clone | nutrition conditional phenotype, suppressible by Ilp2UAS.cBa/Scer\GAL4ey.PU

    Pten117 has increased cell growth | somatic clone | nutrition conditional phenotype, suppressible by Tsc1Q87X

    Pten117 has visible | somatic clone phenotype, suppressible | partially by foxo25

    NOT suppressed by
    Statement
    Reference
    Enhancer of
    Suppressor of
    NOT Suppressor of
    Statement
    Reference
    Other
    Phenotype Manifest In
    Enhanced by
    Suppressed by
    Statement
    Reference

    Pten117 has eye | somatic clone | nutrition conditional phenotype, suppressible by bskDN.UAS/Scer\GAL4Act5C.PP

    Pten117 has eye | somatic clone phenotype, suppressible | partially by InR05545

    Pten117 has eye | nutrition conditional phenotype, suppressible by Akt1

    Pten117 has eye phenotype, suppressible by Akt1

    Pten117 has eye | nutrition conditional phenotype, suppressible by Akt3

    Pten117 has eye phenotype, suppressible by Akt3

    Pten117 has eye phenotype, suppressible by Tor2L19

    Pten117 has eye | somatic clone | nutrition conditional phenotype, suppressible by Ilp2UAS.cBa/Scer\GAL4ey.PU

    Ptendj189/Pten117 has eye phenotype, suppressible by Akt1/Akt3

    Ptendj189/Pten117 has rhabdomere phenotype, suppressible by Akt1/Akt3

    Pten117 has adult head phenotype, suppressible by TorEP2353/Scer\GAL4[-]

    NOT suppressed by
    Statement
    Reference

    Pten117 has eye | somatic clone phenotype, non-suppressible by S6kl-1/S6kl-1

    Enhancer of
    Suppressor of
    Statement
    Reference
    Other
    Statement
    Reference

    Akt1/Akt3, Ptendj189/Pten117 has lipid particle & nurse cell phenotype

    Additional Comments
    Genetic Interactions
    Statement
    Reference

    Expression of bskDN.Scer\UAS in Pten117 eye clones (using the MARCM system) efficiently blocks apoptosis and enhanced the overgrowth phenotype.

    A InR05545 mutant background only slightly reduces the overgrowth found in Pten117 mutant eye clones.

    An Akt11 or Akt13 mutant background completely suppresses the Pten117 overgrowth phenotype, under normal as well as under starvation conditions.

    Reduction of TORC1 through expression of Tsc1Scer\UAS.cTa and gigScer\UAS.cTa (under the control of Scer\GAL4GMR.PU) suppresses the overgrowth of Pten117 mutant tissue.

    Eyes mutant for Pten117 and Tor2L19 are reduced to the size of control eyes at both fed and starved conditions, indicating that the overgrowth of Pten117 clones depends on normal TORC1 function.

    Expression of slifUY681 in Pten117 mutant clones results in a slight reduction of the mutant tissue under normal conditions. Under starvation conditions (10g/l yeast), these double mutant cells are almost completely eliminated. This loss of Pten117 mutant tissue is accompanied by a massive increase in apoptosis. The structure of adult eyes in these mutants are wild-type, indicating that the surrounding tissue is able to compensate for the loss of the clones.

    Knockdown of Atg5, through expression of Atg5dsRNA.Scer\UAS, does not impact on the initial growth of Pten117 clones with reduced slif function (through expression of slifUY681).

    Expression of Ilp2Scer\UAS.cBa under the control of Scer\GAL4ey.PU suppresses the overgrowth found in Pten117 mutant clones under starvation conditions. Furthermore, expression of Ilp2Scer\UAS.cBa restores the growth of both the tissue surrounding the Pten117 clone and peripheral tissue.

    The introduction of Tsc1Q87X clones into the neighborhood of Pten117 clones reduces the overgrowth phenotype, under starvation conditions. Thus, even when neighboring with a tissue that also has a growth advantage, Pten clones themselves experience competition for common resources.

    The generation of Pten117 and Tor2L19 sister clones results in eyes that are completely composed of Pten mutant tissue. However, these eyes are smaller than those without Tor2L19 mutant sister clones.

    Ubiquitous expression of ImpL2Scer\UAS.cHa (under the control of Scer\GAL4Act5C.PP) results in the overgrowth of Pten117 clones, irrespective of whether they neighbor Tor2L19 mutant or wild-type cells. The overgrowth of Pten117 clones causes a further reduction in body size, as evidenced by decreased shoulder width.

    Ras85DV12.Scer\UAS Pten117 double mutant clones generated under the control of Scer\GAL4repo.PU are overgrown and invasive. Cells from mutant clones appear to invade the brain, typically following fibre tracts, and sometimes inducing the formation of trachea. Mutant cells often penetrate deep into the brain. Smaller clones are commonly seen that are composed of relatively differentiated, enlarged glia with diffusely invasive projections.

    Ras85DV12.Scer\UAS Pten117 double mutant optic lobe clones generated using eyFLP under the control of Scer\GAL4repo.PU contain more excess glial cells than in either mutant alone. The clones are composed of 10s of glial cells in third instar larvae, becoming large invasive tumors composed of hundreds to thousands of cells in adults.

    Egfr2.A887T.Scer\UAS Pten117 double mutant clones generated under the control of Scer\GAL4repo.PU are overgrown and invasive. Cells from mutant clones appear to invade the brain, typically following fibre tracts, and sometimes inducing the formation of trachea. Mutant cells often penetrate deep into the brain. Smaller clones are commonly seen that are composed of relatively differentiated, enlarged glia with diffusely invasive projections.

    Egfr2.A887T.Scer\UAS Pten117 double mutant clones generated using eyFLP under the control of Scer\GAL4repo.PU contain more excess glial cells than in either mutant alone. The clones are composed of 10s of glial cells in third instar larvae, becoming large invasive tumors composed of hundreds to thousands of cells in adults.

    btl::EgfrScer\UAS.T:λ\cI-DD Pten117 double mutant clones generated under the control of Scer\GAL4repo.PU are overgrown and invasive. Cells from mutant clones appear to invade the brain, typically following fibre tracts, and sometimes inducing the formation of trachea. Mutant cells often penetrate deep into the brain. Smaller clones are commonly seen that are composed of relatively differentiated, enlarged glia with diffusely invasive projections.

    btl::EgfrScer\UAS.T:λ\cI-DD Pten117 double mutant clones generated using eyFLP under the control of Scer\GAL4repo.PU contain more excess glial cells than in Pten117 alone. The clones are composed of 10s of glial cells in third instar larvae, becoming large invasive tumors composed of hundreds to thousands of cells in adults.

    The rhabdomere defects seen in Pten117/Ptendj189 mutant fly eyes are rescued in a Akt11/Akt13 mutant background. In these animals photoreceptor cell morphology is close to wild-type and eyes display a low frequency of deformed rhabdomeres.

    The nurse cells of Ptendj189/Pten117; Akt13/Akt11 viable females show normal lipid storage, while clones of Pten alleles show formation of large lipid droplets.

    Pten117 ; Akt11/Akt13 photoreceptors have normal morphology and an electroretinogram similar to wild type using a normal PDA paradigm.

    The small rough eye phenotype see in flies with Rheb2D1 somatic clones throughout the eye disc generated using Scer\FLP1ey.PN and Scer\FRT, is largely suppressed by Pten117/Pten117.

    Mosaic flies in which the head is doubly mutant for InR327 and Pten117 have heads which are almost the size of heads singly mutant for Pten117.

    Eye overgrowth caused by somatic clones of Pten117 in the developing eye and the increase in ommatidia size within the clones are not suppressed in homozygous S6kl-1 animals.

    Heads that are doubly mutant for Pten117 and lilli4U5 are smaller than those of Pten117 single mutants and wild-type flies.

    The head defect seen in Pten117 flies is suppressed by TorEP2353.

    Xenogenetic Interactions
    Statement
    Reference

    Expression of BacA\p35Scer\UAS.cHa in Pten117 eye clones (using the MARCM system) efficiently blocks apoptosis and enhanced the overgrowth phenotype.

    Expression of BacA\p35Scer\UAS.cHa in the dorsal half of the eye under the control of Scer\GAL4mirr-DE blocks apoptosis, results in Pten117 clones overgrowing even more in the dorsal compartment.

    Blocking apoptosis, through expression of BacA\p35Scer\UAS.cHa in Pten117 clones with diminished slif function (through expression of slifUY681), delays the collapse of the clones but they are absent from adult eyes.

    Complementation and Rescue Data
    Comments
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    Mutant
    Wild-type
    Stocks (2)
    Notes on Origin
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    External Crossreferences and Linkouts ( 0 )
    Synonyms and Secondary IDs (8)
    References (24)