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General Information
Symbol
Dmel\scrib1
Species
D. melanogaster
Name
FlyBase ID
FBal0103577
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
scrb1, scribble1
Nature of the Allele
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
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 )
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 

Clonal expression of Ras85DV12.UAS in a scrib1 background results in malignant tumors that display the main hallmarks of human metastatic cancers.

Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

scrib1 larval wing discs exhibit tumors, and obvious apoptosis (Dcp1 staining).

The wing discs of scrib1 mutant larvae present tumors, which are formed of cells with severe polarity defects, as compared to controls.

scrib1 mutant MARCM clones induced in the eye-antennal disc are significantly smaller compared to control clones in third instar larvae.

Type II neuroblast lineage MARCM clones mutant for scrib1 are harder to recover than control wild-type clones in third instar larvae and frequently very small. The asymmetric localization of major asymmetric cell division regulators in metaphase/anaphase NBs frequently fails in the mutant clones. scrib1 clones in the antennal imaginal discs occasionally overgrow.

scrib1/+ flies exhibit enhanced memory after conditioning in an olfactory conditioning assay, as compared to controls.

scrib1/scrib1 mutant eye clones show a tumor-like overgrowth phenotype.

scrib1 homozygosity leads to the formation of large tumors in the third instar larval wing disc.

 :scrib1 mutant larvae display a severe increase in the density of circulating hemocytes, as compared to controls.

scrib1/scrib1 mutant clones in the eye-antennal disc are smaller than wild type clones due to increased cell death.

Induction of homozygous clones in the eye-antennal disc results in approximately 10% pupal lethality.

Homozygous clones induced in the eye-antennal disc are eliminated when surrounded by wild-type cells. Dying cells within these clones are largely restricted to boundaries between mutant and wild-type populations (87.2% of dying cells). Most of these dying cells are seen to be detached from their clones and incorporated into the neighbouring wild-type population. A significant number of the mutant cells are fragmented after incorporation into the wild-type population and they appear to be completely internalised into the wild-type cells.

scrib1 mutant eye-antennal disc clones lose apical-basal polarity and die. scrib1 mutant cells are mostly absent from the adult eye and the eye appears normal in size.

The wing discs in scrib1 mutant larvae are overgrown.

scrib1 mutant adult Malpighian tubule clones are significantly enlarged compared to wild-type clones. The mitotic index is increased compared to controls. Mutant clusters typically contain proportionally more renal and nephric stem cells (RNSCs) and renablasts (RBs) compared to control clones. Disrupted cell polarity is observed in mutant cells.

scrib1 clones generated in developing wing discs are completely eliminated by adulthood, and the wing maintains tissue integrity.

scrib1 clones generated in the developing eye-antennal disc are eliminated during development, but a small number of mutant clones do survive into adulthood.

Females carrying homozygous germline clones are fertile.

Homozygous clones in the adult germ cells do not result in defects in the fusome.

Clones of cells mutant for scrib1 do not proliferate as well as wild-type cells but exhibit a cell polarity defect.

Clones of scrib1 eye/antennal imaginal disc cells give rise to a mild tumor phenotype with no detectable invasiveness.

Only 65% of homozygous stage 15 telophase neuroblasts divide asymmetrically.

scrib1/scrib5 adults show defects in thorax closure.

scrib1/scrib673 transheterozygous wing discs show a dramatic increase in both the surface area and volume compared to wild type.

Animals with eyes homozygous for scrib1 never eclose, instead dying as headless pharate adults.

Adherens junctions are mislocalized and septate junctions are absent in scrib1/scrib673 transheterozygous wing discs.

Neuroblasts in homozygous stage 15 embryos (lacking zygotic scrib function) show defects in division; 65% undergo normal division, 31% undergo a symmetrical division and 4% undergo an inverted asymmetrical division. Neuroblasts in stage 15 embryos derived from germline clones (lacking both maternal and zygotic scrib function) show defects in division; 74% undergo normal division, 22% undergo a symmetrical division and 4% undergo an inverted asymmetrical division.

When mutant somatic clones are made in the eye disc, the mutant cells lose their monolayered and columnar shape to become rounded and multilayered. Many (but not all) mutant cells are defective in their ability to initiate differentiation. The regular spacing of ommatidia in the tissue immediately surrounding clones is also often disrupted. Ectopic DNA replication and mitoses are also seen. Little mutant tissue survives to become part of the adult eye. There are often signs of necrosis, especially in the middle of the eye. Increased apoptosis is seen in the third instar larval eye.

scrib1 clonal patches in the eye disc (generated using MARCM) exhibit disrupted differentiation of photoreceptor cells.

In scrib1 mutant clones, the columnar, monolayered epithelial cells become rounded and multilayered, suggesting the cells have lost apical-basal polarity.

Less than 9% of scrib1/scribj7B3 mutant larvae survive to pupation.

At the third instar stage of larval development, scrib1/scribj7B3 mutants fail to pupate and continue to grow to form giant larvae. The third instar imaginal wings taken from scrib1/scribj7B3 mutants show loss of monolayered structure and growth in three dimensions.

scribsmi97B/scrib1 adults show a significantly lower avoidance response to benzaldehyde compared to controls.

Homozygous clones in the eye disc grow poorly and do not invade other tissues. The basement membrane is smooth and continuous on the outer surface of eye discs containing homozygous clones. Marked clones in scrib1/Df(3R)Tl-X eye discs grow poorly and do not invade other tissues.

scrib1 mutants exhibit a statistically significant increase in synaptic basal lamina thickness compared to wild-type.

Imaginal discs of late third instar homozygous larvae are profoundly disorganised and massively overgrown, containing 4.7 times as many cells as wild-type discs. The discs consist of spherical masses of tightly packed cells as opposed to the folded monolayer epithelium seen in wild-type larvae. Overgrowth of brain tissue is also seen; the brain lobes are much larger than normal and the axon-rich medulla is disorganised.

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

scrib1 has hyperplasia phenotype, suppressible by hepr75

NOT suppressed by
Statement
Reference
Enhancer of
NOT Enhancer of
Statement
Reference

scrib1 is a non-enhancer of visible phenotype of RetMEN2B.GMR

Suppressor of
Statement
Reference

scrib1 is a suppressor of visible phenotype of RetMEN2A.GMR

scrib[+]/scrib1 is a suppressor | partially of visible phenotype of CycEJP

NOT Suppressor of
Statement
Reference
Other
Statement
Reference

l(2)36Fd1/l(2)36Fd[+], scrib1/scrib5 has lethal phenotype

S(CycE[JP])2.4[+]/S(CycEJP)2.457S6, scrib1/scrib5 has lethal phenotype

S(CycE[JP])2.9[+]/S(CycEJP)2.925S11, scrib1/scrib5 has lethal phenotype

S(CycEJP)2.9E1S4/S(CycE[JP])2.9[+], scrib1/scrib5 has lethal phenotype

l(2)gl[+]/l(2)gl4, scrib1/scrib5 has lethal phenotype

Phenotype Manifest In
Enhanced by
Suppressed by
Statement
Reference

scrib1 has wing disc phenotype, suppressible by DefSK3

scrib1 has eye | somatic clone phenotype, suppressible by DCAF12UAS.cHa

scrib1 has wing disc phenotype, suppressible by egr3/egr3

scrib1 has wing disc phenotype, suppressible by hepr75

NOT suppressed by
Enhancer of
NOT Enhancer of
Statement
Reference

scrib1 is a non-enhancer of eye phenotype of RetMEN2B.GMR

Suppressor of
Statement
Reference

scrib1 is a suppressor of eye phenotype of RetMEN2A.GMR

scrib[+]/scrib1 is a suppressor | partially of eye phenotype of CycEJP

NOT Suppressor of
Statement
Reference

scrib1 is a non-suppressor of eye phenotype of RetMEN2B.GMR

Other
Statement
Reference

Ras85DV12.UAS, Scer\GAL4Act5C.PI/Scer\GAL4Act5C.PI, scrib1 has basal lamina & eye disc | somatic clone phenotype

Additional Comments
Genetic Interactions
Statement
Reference

scrib1 homozygous eye disc clones that also express either rlWT.UAS, rlR80S.UAS, rlD334N.UAS.cKa or rlD334N.UAS.cKa (under the control of Scer\GAL4Act5C.PI) are larger than clones only homozygous for scrib1; scrib1 homozygous antennal disc clones are readily visible on the rlR80S.UAS-, rlD334N.UAS.cKa and rlD334N.UAS.cKa- expressing conditions, but hardly detected in the rlWT.UAS-expressing condition. In agreement, individuals bearing such double mutant clones show abdominal accumulation the rlR80S.UAS-, rlD334N.UAS.cKa and rlD334N.UAS.cKa- expressing conditions, but not in the rlWT.UAS-expressing condition.

Third instar larval eye-antennal imaginal disc clones homozygous for scrib1 and expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU form invasive tumors; the presence of these clones in egr1/egr3 transheterozygotes, or additional clonal homozygosity for kay3, or additional clonal co-expression of Ets21CKK103211 in combination with kaydsRNA.Scer\UAS.cUa do not lead to significant cell non-autonomous induction of autophagosomes (assessed by a Atg8a fluorescence reporter) in neighboring disc cells.

The small size of scrib1 mutant MARCM clones that are recovered in third instar larval eye-antennal discs is significantly rescued if the clones also express fmtScer\UAS.cMa under the control of Scer\GAL4Scer\FRT.Act5C.

The small size of Type II neuroblast lineage MARCM clones mutant for scrib1 in third instar larvae can be rescued by expression of bskDN.Scer\UAS under the control of Scer\GAL4Dll-md23 in the mutant clones, these clones are also recovered more frequently than scrib1-only mutant clones. scrib1 clones expressing Ras85DV12.Scer\UAS can be recovered at a similar rate as wild-type ones and instead of a single neuroblast they frequently contain 2 or 3 but the clones do not show significant overgrowth.

scrib1 mutant clones in larval antennal discs occasionally display overgrowth, clones double mutant for both scrib1 and cnoR2 frequently show clear tumorigenic overgrowth, while scrib1 clones expressing Ras85DV12.Scer\UAS (under the control of Scer\GAL4Dll-md23) are all tumor-like.

Type II neuroblast lineage MARCM clones double mutant for cnoR2 and scrib1 display a strong tumor-like overgrowth with clone areas significantly larger than either of the single mutant clones or the control wild-type clones in third instar larvae. The cnoR2;scrib1 clones are composed of almost exclusively of progenitor cells (dpn-positive) with few differentiated cells and in respect to overgrowth capacity fall into two categories - about half of the clones does not overgrow while the other half does, about a third of which massively so. The double mutant clones contain significantly more neuroblast and intermediate neural progenitor (INP) cells compared to wild-type clones but the relative proportion of mature INPs is reduced (although their absolute number per clone is also increased). The asymmetric localization major asymmetric cell division regulators in metaphase/anaphase NBs fails in all the mutant clones. The overgrowth and increased number of progenitor cells characteristic for cnoR2;scrib1 clones is significantly suppressed by Scer\GAL4Dll-md23-driven expression of Ras85DKK108029, cnoScer\UAS.cBa or Akt1KK100495, but not cnoΔN.Scer\UAS or RafKK100982 in the mutant clones.

scrib1/scrib1;DCAF12Δ1/DCAF12Δ1 double mutant clones show increased tissue overgrowth and scrib1/scrib1 mutant clones overexpressing DCAF12Scer\UAS.cHa show enhanced tissue integrity (compared to scrib1/scrib1 clones).

scrib1 eye discs expressing Ras85DV12.Scer\UAS in clones show a dramatic tumour-like overgrowth and metastasis.

The tumor phenotype of scrib1 homozygous third instar larval wing discs is suppressed by hepr75 hemizygosity or ykiB5 heterozygosity.

Transplanted scrib1 mutant eye disc fragments expressing MARCM closes of Ras85DV12.Scer\UAS grow continuously and induce distinctive bloating of the abdomen before killing the host. Wild-type discs grow only a limited amount before ceasing, and the transplanted host survives for weeks. Metastasis-like events are rare for the tumors. However, all the tumor-bearing hosts show robust wasting phenotypes in tissues distant from the transplant. Transplanted wild-type disc fragments do not induce these phenotypes. Cachexia-like wasting is observed in adipose tissue (fat body), muscle, and ovaries. Comparison of food consumption in wild-type and tumor-bearing hosts show that he tumor-induced wasting is not due to decreased food consumption (anorexia).

The proportion of hemisegments with abnormal number of neurons in the asymmetrically dividing RP2 neural lineage is significantly increased in wtsx1/+;scrib1/+ double heterozygous embryos compared to either of the single heterozygotes or wild type.

The majority of larvae with scrib1 mutant eye-antennal disc clones expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU exhibit defective photoreceptor differentiation, and developmental arrest as third instar giant larvae and die; only a few individuals form pseudopuparia and are developmentally delayed, starting on day 8 after egg laying. The cells of scrib1 mutant eye-antennal disc clones expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU are highly invasive, penetrating the ventral nerve cord of a majority of developmentally arrested larvae.

Clonal co-expression of Ets21CKK103211 partially suppresses the lethality and developmental delay seen in larvae with scrib1 mutant eye-antennal disc clones expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU, but fails to suppress the invasive infiltration of the ventral nerve cord exhibited by cells of these clones.

Clonal co-expression of ftz-f1JF02738 or kayN-Ala.Scer\UAS, or addition of a clonal kay3 mutation, but not co-expression of JradsRNA.Scer\UAS, partially suppresses the lethality and developmental delay seen in larvae with scrib1 mutant eye-antennal disc clones expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU, and suppresses the invasive infiltration of the ventral nerve cord exhibited by cells of these clones, although the tumor mass is not significantly decreased.

Larvae with scrib1 mutant eye-antennal disc clones expressing ftz-f1JF02738, Ets21CKK103211, and Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU reach pupation faster than larvae with scrib1 mutant eye-antennal disc clones expressing ftz-f1JF02738 and Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU, or those with scrib1 mutant eye-antennal disc clones expressing Ets21CKK103211 and Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU.

Clonal co-expression of kayN-Ala.Scer\UAS, or addition of a clonal kay3 mutation, but not co-expression of JradsRNA.Scer\UAS or ftz-f1JF02738, partially suppresses the defective photoreceptor differentiation seen in scrib1 mutant eye-antennal disc clones expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU.

Larvae with scrib1, kay3 mutant eye-antennal disc clones expressing Ras85DV12.Scer\UAS and Ets21CKK103211 under the control of Scer\GAL4Act.PU exhibit suppression of larval lethality as compared to either larvae with scrib1, kay3 mutant eye-antennal disc clones expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU, or those with scrib1 mutant eye-antennal disc clones expressing Ras85DV12.Scer\UAS and Ets21CKK103211 under the control of Scer\GAL4Act.PU; but these larvae still exhibit pupal lethality.

Adults with scrib1 mutant eye-antennal disc clones expressing Ras85DV12.Scer\UAS and ftz-f1JF02738 under the control of Scer\GAL4Act.PU exhibit a rough eye that is increased in size, and contains fewer clonally-derived ommatidia, as compared to controls.

The increased density of circulating hemocytes observed in in scrib1 larvae is suppressed by egr3 homozygosity.

Somatic clones (induced specifically in the eye disc) expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU and homozygous mutant for scrib1 show substantial tumorigenic overgrowth but do not form secondary tumors although floating clone cells are frequently observed in the hemolymph.

The egr1/egr3 background fully suppresses the increased cell death seen in eye-antennal disc scrib1/scrib1 mutant clones, and also leads to overgrowth of these clones.

Ras85DV12.Scer\UAS scrib1 tumour cells fail to differentiate into neurons.

Loss of cher markedly interferes with the growth of Ras85DV12.Scer\UAS scrib1 tumours. The loss of cher does not affect the level of apoptosis in either the clonal nor the surrounding eye-antennal imaginal disc, indicating that loss of cher does not affect tumour cell viability.

Eye-antennal imaginal discs carrying Ras85DV12.Scer\UAS scrib1 cher1 clones display extra cell divisions, mainly occurring in the surrounding non-clonal tissue. Despite sizeable Ras85DV12.Scer\UAS scrib1 cher1 clones clones located posterior to the morphogenetic furrow, the number of elav-positive differentiating photoreceptors increases and their organization is better than in Ras85DV12.Scer\UAS scrib1 clones. Consequently, well-ordered arrays of ommatidia appear in Ras85DV12.Scer\UAS scrib1 cher1 eye-antennal imaginal discs compared with the indiscernible pattern in Ras85DV12.Scer\UAS scrib1 discs.

Many apically localised Ras85DV12.Scer\UAS scrib1 cells are elongated.

Cross-sections of Ras85DV12.Scer\UAS scrib1 cher1 eye-antennal discs reveals that large tumours only reside within the basal compartment of the columnar epithelium. Smaller Ras85DV12.Scer\UAS scrib1 cher1 clones are confined between the squamous peripodial epithelium and the columnar epithelium.

In contrast to highly invasive Ras85DV12.Scer\UAS scrib1 clonal tumours, fewer Ras85DV12.Scer\UAS scrib1 cher1 clones invaded the brain and the ventral nerve cord. Expression of cherKK107518 suppresses the tumour invasiveness found in Ras85DV12.Scer\UAS scrib1 clones.

Larvae bearing Ras85DV12.Scer\UAS scrib1 tumours all die in the third instar and never pupate. In contrast, on day 8-9 after egg laying, 30% of Ras85DV12.Scer\UAS scrib1 cher1 larvae begin to wander and pupate, albeit 2-3 days later than control animals. Thirty percent of Ras85DV12.Scer\UAS scrib1 cher1 pupape emerge as adults. These adult flies exhibit abnormally enlarged eyes with a folded surface, accommodating surplus ommatidia.

Expression of zipGD1566 lessens the invasiveness of Ras85DV12.Scer\UAS scrib1 tumours and improves pupation rate.

Ras85DV12.Scer\UAS-scrib1 mutant larval MARCM clones exhibit tissue overgrowth. Exposure to acivicin restrains Ras85DV12.Scer\UAS-scrib1 tumor overgrowth.

Knockdown of CTPsyn, through expression of CTPsynGD4740, induces a strong, significant reduction in tumor growth in Ras85DV12.Scer\UAS-scrib1 mutant larval MARCM clones.

Knockdown of CG9674, through expression of CG9674GD14285, induces a strong, significant reduction in tumor growth in Ras85DV12.Scer\UAS-scrib1 mutant larval MARCM clones.

Knockdown of bur, through expression of burGD13797, induces a reduction in tumor growth in Ras85DV12.Scer\UAS-scrib1 mutant larval MARCM clones.

Knockdown of r, through expression of rGD9607, induces a reduction in tumor growth in Ras85DV12.Scer\UAS-scrib1 mutant larval MARCM clones.

Knockdown of ade2, through expression of ade2GD1356, induces a reduction in tumor growth in Ras85DV12.Scer\UAS-scrib1 mutant larval MARCM clones.

Knockdown of Gfat1, through expression of Gfat1GD7732, induces a reduction in tumor growth in Ras85DV12.Scer\UAS-scrib1 mutant larval MARCM clones.

Knockdown of Prat, through expression of PratGD9838, induces a reduction in tumor growth in Ras85DV12.Scer\UAS-scrib1 mutant larval MARCM clones.

Knockdown of Prat2, through expression of Prat2GD16167, induces a reduction in tumor growth in Ras85DV12.Scer\UAS-scrib1 mutant larval MARCM clones.

Knockdown of CG9940, through expression of CG9940GD14730, induces a reduction in tumor growth in Ras85DV12.Scer\UAS-scrib1 mutant larval MARCM clones.

Expression of either bskdsRNA.Scer\UAS, bskDN.Scer\UAS, Traf6dsRNA.Scer\UAS or Ced-12dsRNA.Scer\UAS under the control of Scer\GAL4Act.PU in the cells surrounding scrib1 clones in the eye-antennal disc significantly suppresses the elimination of the mutant scrib1 clones compared to that seen when the cells surrounding the clone are wild type.

Expression of either PvrScer\UAS.cDa or egrScer\UAS.cIa under the control of Scer\GAL4Act.PU in the cells surrounding scrib1 clones in the eye-antennal disc significantly enhances the elimination of the mutant scrib1 clones compared to that seen when the cells surrounding the clone are wild type.

Expression of egrIR.Scer\UAS under the control of Scer\GAL4Act.PU only within scrib1 clones in the eye-antennal disc results in 30.7% pupal lethality, while expression of egrIR.Scer\UAS under the control of Scer\GAL4Act.PU both within scrib1 clones in the eye-imaginal disc and in the surrounding wild-type cells results in 51.3% pupal lethality.

In an egr1 mutant background, scrib1 mutant clones in the eye-antennal disc are no longer eliminated, but grow aggressively and develop into tumours. In this background, expression of egrScer\UAS.cIa under the control of Scer\GAL4Act.PU only in the cells surrounding the scrib1 clones reverses the tumour phenotype; the scrib1 clones do not overgrow and are out-competed by the surrounding cells.

Expression of PvrdsRNA.Scer\UAS.cRa under the control of Scer\GAL4Act.PU in the cells surrounding scrib1 clones in the eye-antennal disc significantly suppresses the elimination of the mutant scrib1 clones compared to that seen when the cells surrounding the clone are wild type.

scrib1 mutant eye-antennal disc clones that simultaneously express Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU grow into large metastatic tumors. Wild type cells are almost completely absent from late Ras85DV12.Scer\UAS scrib1 tumors.

Eye-antennal disc clones that express Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU, and in which adjacent cells are mutant for scrib1, develop into large tumors capable of invading the ventral nerve cord. In the late stages of tumor development most cells in the tumor mass are Ras85DV12.Scer\UAS cells and scrib1 cells and wild type cells are almost completely absent.

Stat92E06346 partially suppresses the overgrowth and invasion of the nerve cord seen in scrib1 mutant eye-antennal disc clones that simultaneously express Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU.

Expression of domeΔCYT.Scer\UAS suppresses the overgrowth and invasion of the nerve cord seen in scrib1 mutant eye-antennal disc clones that simultaneously express Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU.

Expression of domeΔCYT.Scer\UAS in eye-antennal disc clones that express Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU, and in which adjacent cells are mutant for scrib1, suppresses the overgrowth and invasion of the nerve cord.

No tumors are seen when upd1Scer\UAS.cUa is expressed under the control of Scer\GAL4Act.PU in scrib1 mutant eye-antennal clones.

No tumors are seen when upd1Scer\UAS.cUa is expressed under the control of Scer\GAL4Act.PU in wild type eye-antennal disc cells that are adjacent to scrib1 mutant cells.

The eye is reduced in size when scrib1 mutant clones are generated in eye-antennal discs in which adjacent cells are mutant for Stat92E06346.

Expression of bskDN.Scer\UAS in eye-antennal disc clones that express Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU, and in which adjacent cells are mutant for scrib1, partially suppresses the tumor phenotype. Few scrib1 cells remain in the tissue at late stages.

Expression of bskDN.Scer\UAS suppresses the tumors seen in scrib1 mutant eye-antennal disc clones that simultaneously express Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU.

Stat92E06346 in eye-antennal disc clones that express Ras85DV12.Scer\UAS under the control of Scer\GAL4Act.PU, and in which adjacent cells are mutant for scrib1, partially suppresses the overgrowth and completely abrogates the invasion of the nerve cord.

Hemizygous hepr75 suppresses the wing disc tumors seen in scrib1 mutant larvae.

Ras85DΔC40B, scrib1 double mutant adult Malpighian tubule clones display only a few differentiated renalcytes (RCs), like the single Ras85DΔC40B mutant phenotype.

Heterozygosity for scrib1 enhances the frequency of ommatidia that show planar cell polarity defects in Vangstbm-153 homozygotes.

scrib1 mutant clones survive in egr1 mutant eye-antennal discs background. Overgrowth of double mutant cells is observed, and tumor development is observed in pupal eye-antennal tissue. scrib1 mutant clones generated in egr1 mutant wing discs also survive, and tumor development is observed in the wing disc.

Tumour formation and animal lethality are both completely rescued by over-expression of egrScer\UAS.cIa under the control of Scer\GAL4Act5C.PI in scrib1, egr1 double mutant clones.

Expression of egrScer\UAS.cIa under the control of Scer\GAL4Act5C.PI in scrib1 somatic mutant clones results in a reduction in the size of the clones by 86.5%, and mutant clones are not evident in adult eyes.

Expression of Rab5S43N.Scer\UAS under the control of Scer\GAL4Act5C.PI in scrib1 somatic mutant clones results in aggressive overgrowth of eye-antennal disc mutant tissue.

Clones in the eye antennal disc which are expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C and are also homozygous for scrib1 show invasive behaviour, invading the ventral nerve cord. These clones show degradation of the basement membrane.

Co-expression of bskDN.Scer\UAS suppresses the invasive behaviour of clones in the eye antennal disc which are expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C and are also homozygous for scrib1.

The invasive behaviour of clones in the eye antennal disc which are expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C and are also homozygous for scrib1 is partially suppressed in a Mmp1Q273 homozygous background.

The invasive behaviour and degradation of the basement membrane of clones in the eye antennal disc which are expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C and are also homozygous for scrib1 is suppressed if the clones are also co-expressing both ReckScer\UAS.cSa and TimpScer\UAS.cSa simultaneously.

Expression of Ras85DV12.Scer\UAS in scrib1 mutant clones results in massive and metastatic tumours. After 6 days the cells exhibit moderate tumour growth and ventral nerve cord invasion phenotypes. Co-expression of bskDN.Scer\UAS and Ras85DV12.Scer\UAS in scrib1 mutant clones completely blocks the invasion of the ventral nerve cord as well as secondary tumour foci formation.

The presence of an Akt11 mutant background considerably reduces the tumour load in scrib1 mutant clones expressing Ras85DV12.Scer\UAS (under the control of Scer\GAL4Act5C.PI) using the FLP/FRT system but does not impair metastatic behaviour.

Overexpression of Akt1Scer\UAS.T:Ivir\HA1 (under the control of Scer\GAL4Act5C.PI) using the FLP/FRT system in brain somatic clones mutant for scrib1 and wtsx1 does not cause metastatic behaviour despite accelerated tumour growth.

Clones of eye/antennal imaginal disc cells that express Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C.PI and are also homozygous for scrib1 show an enhancement of the tumorigenic phenotype seen in clones that are mutant for either scrib1 or express Ras85DV12.Scer\UAS. The Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, scrib1 cells become invasive; at 6 days after egg laying, imaginal disc cells appear in the ventral nerve cord (VNC). At day 9, the invading cells obscure the eye/antennal discs, brain lobes, and the VNC so these anatomical structures are no longer distinguishable. The invading tumor cells are morphologically distinct and have a prominent actin cytoskeleton network typical of cells undergoing movement or shape change.

Animals bearing Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, scrib1 clones progress normally through larval development but fail to pupate and die as third instar larvae and around day 13 AEL.

Expression of bskDN.Scer\UAS clones blocks the cell invasive phenotype of Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, scrib1 eye/antennal imaginal disc clones. These clones still overgrow in the discs but never leave this structure. bskDN.Scer\UAS expression also rescues the larval lethality of Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, scrib1 clone-bearing animals, with rescued animals progressing through most of metamorphosis and dying as pharate adults.

Expression of pucScer\UAS.cMa in Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, scrib1 eye/antennal imaginal disc clones prevents the invasion cell phenotype but does not rescue the overgrowth of the eye/antennal imaginal disc clones. pucScer\UAS.cMa expression rescues the larval lethality of Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, scrib1 clone-bearing animals and partially restores pupariation.

scrib1 eye/antennal imaginal disc clones grow larger in size when they express kaydsRNA.Scer\UAS under the control of Scer\GAL4Act5C.PI. Apoptosis is suppressed in the Scer\GAL4Act5C.PI>kaydsRNA.Scer\UAS; scrib1 clones.

Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, TimpScer\UAS.cPa, scrib1 eye/antennal disc clones produce a tumor mass larger than that seen in Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, scrib1 disc clones. However, the tumor cell invasiveness observed in Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, scrib1 clones is suppressed by expression of TimpScer\UAS.cPa.

Expression of either Mmp1dsRNA.Scer\UAS or Mmp2dsRNA.Scer\UAS in Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, scrib1 eye/antennal imaginal disc clones significantly suppresses the cell invasiveness phenotype but does not suppress the formation of tumors within the disc. Coexpression of Mmp1dsRNA.Scer\UAS and Mmp2dsRNA.Scer\UAS further reduces the invasiveness of Scer\GAL4Act5C.PI>Ras85DV12.Scer\UAS, scrib1 cells.

Downregulation of JNK signaling in clones of scrib1 mutant tissue by overexpression of bskK53R.Scer\UAS suppresses apoptosis (from 16.6% to wild-type levels of 25%) and increases the overgrowth of the tissue, even compared to wild-type, resulting in scrib1 bskK53R.Scer\UAS clones contributing over 70% of the tissue in third instar eye imaginal discs.

Clones of eye imaginal discs that express phlScer\UAS.F179 autonomously (under the control of Scer\GAL4Act5C.PI) in scrib1 clones grow into massive and invasive tumours during larval stages, resulting in 80% of animals not pupating and dying as giant larvae.

Expression of hepAct.Scer\UAS in eye imaginal disc clones that express phlScer\UAS.F179 (under the control of Scer\GAL4Act5C.PI) and scrib1 results in adult eyes with massive overgrowth. The heads are significantly bigger and the retina of these mutants are dramatically larger than that of a wild-type eye. In many cases, the retina is folded and bunched to accommodate the surfeit of tissue. These severely hyperplastic eye structures are well patterned and show a distinctive ommatidial organisation. The tumourous overgrowth is induced non-autonomously in the wild-type cells surrounding the hepAct.Scer\UAS phlScer\UAS.F179 (both under the control of Scer\GAL4Act5C.PI) scrib1 cells.

dlg114 ; scrib1/+ neuroblasts show defects in division; 52% undergo normal division, 32% undergo a symmetrical division and 16% undergo an inverted asymmetrical division. dlg114 ; l(2)glunspecified/+ ; scrib1/+ neuroblasts show defects in division; 56% undergo normal division, 22% undergo a symmetrical division and 22% undergo an inverted asymmetrical division.

When bskK53R.Scer\UAS is driven by Scer\GAL4αTub84B.PL in scrib1 clones in the eye, a significant increase in the size of scrib1 clones is seen. However, this combination leads to pupal lethality. When scrib1 clones are made in eyes expressing hidGMR.PG the viability of the mutant clones increases dramatically. This results in tissue overgrowth and lethality. When scrib1 clones are made in regions of eye disc tissue that are l(3)cl-R31 (made by FLP clones in the eye), the scrib1 clone is not eliminated by apoptosis as seen in wild-type tissue but overproliferates, losing recognisable structure, resulting in lethality. When Ras85DV12.Scer\UAS or NICN.Scer\UAS are expressed in scrib1 clones, massive overproliferation of the scrib1 tissue is seen inducing larval/pupal lethality. Co-expression of CycEScer\UAS.cRa with BacA\p35Scer\UAS.cHa in scrib1 clones results in some overgrowth and pupal lethality. Co-expression of DpScer\UAS.cDa with BacA\p35Scer\UAS.cHa in scrib1 clones results in some overgrowth and pupal lethality. The addition of E2f191 or dapScer\UAS.cdNa suppresses the overproliferation phenotype seen in scrib1, Ras85DV12.Scer\UAS, Scer\GAL4αTub84B.PL clones.

Marked clones in the eye disc expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C.PI and which are also homozygous for scrib1 show metastatic behaviour. The basement membrane has many points of discontinuity in eye discs containing clones which are homozygous for scrib1 and which are expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C.PI, and mutant cells spread from these areas. The metastatic behaviour seen in clones in the eye disc which are homozygous for scrib1 and are also expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C.PI is suppressed if they are co-expressing shgScer\UAS.cOa but is not suppressed if they are co-expressing argos::shgi.Scer\UAS.T:Hsap\MYC. The metastatic behaviour seen in clones in the eye disc which are homozygous for scrib1 and are also expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C.PI is not suppressed if they are co-expressing Hsap\CDKN1AScer\UAS.cHa; although the tumour size is decreased, mutant cells can still spread into the ventral nerve cord. Marked clones in the eye disc which are homozygous for scrib1 and are expressing BacA\p35Scer\UAS.cHa under the control of Scer\GAL4Act5C.PI do not show metastatic behaviour. Marked clones in the eye disc which are homozygous for scrib1 and are co-expressing DpScer\UAS.cDa, E2fScer\UAS.cNa and BacA\p35Scer\UAS.cHa under the control of Scer\GAL4Act5C.PI do not show metastatic behaviour. Expression of either dmScer\UAS.cZa or Akt1Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4Act5C.PI in clones in the eye disc which are homozygous for scrib1 increases the amount of mutant tissue compared to scrib1 single mutant clones, but the double mutant clones do not show metastatic behaviour. scrib1 wtsx1 double mutant clones in the eye disc produce tumours which do not show metastatic behaviour. Expression of Akt1Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4Act5C.PI in scrib1 wtsx1 double mutant clones in the eye disc increases tumour size but does not result in metastatic behaviour.

Xenogenetic Interactions
Statement
Reference

When BacA\p35Scer\UAS.cHa is driven by Scer\GAL4αTub84B.PL in scrib1 clones in the eye, the amount of mutant tissue surviving to adulthood increases compared with scrib1 clones alone.

Co-expression of CycEScer\UAS.cRa with BacA\p35Scer\UAS.cHa in scrib1 clones results in some overgrowth and pupal lethality.

Expression of Hsap\ScribScer\UAS.T:Avic\GFP-EGFP (under the control of Scer\GAL4αTub84B.PL) within MARCM-generated scrib1 clones largely restores the differentiation and patterning of the photoreceptors in the eye. Hsap\ScribScer\UAS.T:Avic\GFP-EGFP expression also suppresses the tissue organisation defects associated with scrib1 mutant tissue.

scrib1 mutant clones expressing Hsap\ScribScer\UAS.T:Avic\GFP-EGFP (under the control of Scer\GAL4αTub84B.PL) restores the columnar architecture and monolayer organization of the epithelial cells, while the cytoskeleton appears normal.

Ubiquitous expression of Hsap\ScribScer\UAS.T:Avic\GFP-EGFP (under the control of Scer\GAL4Act.PU) effectively suppresses the larval overgrowth phenotype found in scrib1/scribj7B3 mutants. Expression of Hsap\ScribScer\UAS.T:Avic\GFP-EGFP in scrib1/scribj7B3 mutant third instar imaginal wings suppresses the tumorous overgrowth of the epithelial tissues and allows the formation of a monolayered epithelial structure closely resembling that of wild-type discs.

Expression of Hsap\ScribScer\UAS.T:Avic\GFP-EGFP (under the control of Scer\GAL4Act.PU) rescues larval lethality in scrib1/scribj7B3 mutants to allow 59% to form adult structures (pharate adults) and 23% to eclose as mature adult flies. These adult flies exhibit some developmental defects in the eyes and wings on a proportion of rescued animals as well as ectopic scutellar bristles, suggesting the rescue effect is not fully penetrant. Both sexes appear to be sterile.

Complementation and Rescue Data
Comments

Expression of scribΔCT.Scer\UAS.T:Hsap\MYC or scribScer\UAS.T:Hsap\MYC under the control of Scer\GAL4wor.PA significantly restores normal asymmetric divisions in homozygous scrib1 stage 15 neuroblasts.

Expression of either scribCT.Scer\UAS.T:Hsap\MYC, scribLRR.Scer\UAS.T:Hsap\MYC, scribΔPDZ.Scer\UAS.T:Hsap\MYC, scribPDZ.Scer\UAS.T:Hsap\MYC or scribΔLRR.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4wor.PA fails to restore normal asymmetric divisions in homozygous scrib1 stage 15 neuroblasts.

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