FB2025_01 , released February 20, 2025
Allele: Dmel\l(2)gl4
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General Information
Symbol
Dmel\l(2)gl4
Species
D. melanogaster
Name
FlyBase ID
FBal0009225
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
Lgl4
Key Links
Mutagen
Nature of the Allele
Progenitor genotype
Cytology
Description

Deletion of sequences from 0 to 22kb (coordinates with respect to proximal end of a cloned l(2)gl region, close to the tip of 2L).

Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Variant Molecular Consequences
Associated Sequence Data
DNA sequence
Protein sequence
 
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
model of  carcinoma
model of  cancer
exacerbates  carcinoma
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 

Clonal expression of Ras85DV12.UAS in a l(2)gl4 background results in malignant tumors that display the main hallmarks of human metastatic cancers.

Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In

microtubule & oocyte | germ-line clone

Detailed Description
Statement
Reference

Eye-antennal disc-specific clones that both express Ras85DV12.UAS under the control of Scer\GAL4Act5C.PI and are homozygous for l(2)gl4 form tumors that invade the neighboring ventral nerve cord.

Clones in the pupal dorsal thorax epithelium that are homozygous for l(2)gl4 show some delamination/invasion (i.e. multilayered polarized epithelial cells beneath the epithelial sheet) as well as defective adherens and septate junctions.

Eye-antennal disc clones that both express Ras85DV12.UAS under the control of Scer\GAL4Act.PU and are l(2)gl4-homozygous form tumors.

l(2)gl4 clones generated in the larval eye disc lead to ommatidial rotation phenotypes - i.e. planar cell polarity defects -, particularly in clusters closer to the morphogenetic furrow.

l(2)gl4 embryos display embryos displaying defects in head or head cuticle morphogenesis.

Expression of Scer\GAL4hh.PU>l(2)glASA.Scer\UAS.T:Avic\GFP rescues the cell polarity defects in l(2)gl4/l(2)gl334 mutant wing disc epithelia, but reveals spindle orientation defects.

Expression of Scer\GAL4tub.PU>l(2)glASA.Scer\UAS.T:Avic\GFP rescues the cell polarity defects in l(2)gl4 mutant cells in follicular epithelia, but reveals spindle orientation defects.

Expression of Scer\GAL4hh.PU>l(2)glScer\UAS.T:Uuuu\Myr-Unk rescues the cell polarity defects in l(2)gl4/l(2)gl334 mutant wing disc epithelia, but reveals spindle orientation defects.

Expression of Scer\GAL4tub.PU>l(2)glScer\UAS.T:Uuuu\Myr-Unk rescues the cell polarity defects in l(2)gl4 mutant cells in follicular epithelia, but reveals spindle orientation defects.

In the tumors formed in l(2)gl4 mutant wing disc clones, the tracheal network shows several ectopic branches visible at both the basal and the apical sides of the disc. Tracheal vessels are also included in the disc itself.

The brains of l(2)gl1/l(2)gl4 mutant third instar larvae are enlarged.

l(2)gl4 mutant somatic clones are eliminated from mosaic imaginal disc epithelium by cell competition.

l(2)gl4 mutant clones (in a minute/+ background to alleviate cell competition) display neoplastic transformation in the proximal domain of the wing disc. Apico-basal polarity is lost and the basement membrane breaks down. Distal clones are eliminated from the epithelium after an initial period of survival, because of cell death, and are basally extruded from the wing epithelium. Distal l(2)gl4 mutant clones are unable to delaminate as their basement membrane remains intact.

l(2)gl4 mutant wing disc clones grow preferentially in the proximal-distal direction, similar to wild type clones, and at two days after clone induction they are similar in size to wild type controls. By three days l(2)gl4, mutant clones are half the size of the wild type twin spots and many of them disappear by the end of larval development due to apoptosis. Some persist to the end of development, resulting in scarring of the adult wing. l(2)gl4 mutant clones show slight defects in disc folding but are not strongly compromised in apical-basal polarity. The wild type twins in wing discs containing l(2)gl4 mutant clones are larger in size than in control discs. Clones in the proximal regions (hinge and pleura) are larger than those in the wing pouch, although they never form tumors

An increase in Rab5-positive early endosomes is seen in l(2)gl4 mutant wing disc clones outside of the wing pouch region.

Blocking endocytosis in l(2)gl4 mutant clones results in overgrowth of some clones in the proximal regions of the wing disc (hinge and pleura), but no overgrowth of wing pouch clones, which continue to be smaller than wild type twins and show increased apoptosis.

When l(2)gl4 mutant clones are generated in a Minute background can acquire a competitive advantage: they are able to overgrow and the cells become rounded indicating that apical-basal polarity has been lost. l(2)gl4 mutant clones in the wing pouch do not overgrow and do not undergo apoptosis. Clones in the proximal (hinge and pleura) regions do not show increased apoptosis, but some apoptosis is seen in surrounding cells. The cells lose polarity and the basement membrane shows signs of discontinuity compared with wild type.

l(2)gl4 mutant clones in the ovarian follicular epithelium overproliferate and form multilayers near to the egg chamber poles, extending away from the poles and into the nurse cell territory when allowed to grow for four days. Apoptosis is occasionally observable in egg chambers from stage 8 onwards at the clone border but no autonomous apoptosis is seen.

l(2)gl4 mutant embryos show a strong disruption in tissue architecture.

l(2)gl4 maternal-only mutant embryos display disrupted cell shape. Cell alignment is strongly affected in the denticle-secreting cells. Denticles form in belts that are not properly aligned with the ventral epidermis.

l(2)gl4 maternal/zygotic mutant embryos show a disrupted ventral cuticle. The cuticle has a convoluted appearance and only a few denticles are observed. Epidermal cells completely lack organised shape and alignment, and denticles are absent from the ventral epidermis.

Analysis of homozygous clones in the wing disc shows that by 96 hours after clone induction, a number of homozygous cells abutting wild-type cells have become apoptotic and are basally extruded from the wing disc (some apoptotic cells remain in the epithelial layer). At 144 hours after clone induction, most of the homozygous clones have been basally extruded from the epithelial layer, which is frequently associated with indentations of the epithelial layer. Homozygous cells in clones in the wing disc that are surrounded by Minute/+ cells survive and show an overgrowth phenotype. Basally extruded homozygous cells which are not apoptotic are also sometimes seen.

A convoluted cuticle forms in embryos mutant for l(2)gl4 both maternally and zygotically.

When l(2)gl4/l(2)glts3 flies are cultivated at 27.5[o]C, the temperature-sensitive l(2)glts3 partially loses its activity, and 86% of individual flies successfully develop into adulthood. Approximately 28% of l(2)gl4/l(2)glts3 flies carry at least one defective extrasensory bristle, such as a duplicated bristle or a socket without a bristle, as a result of the partial loss of l(2)gl at the semi-restrictive temperature of 27.5[o]C.

The oocyte nucleus is mislocalised to a lateral position or remains at the posterior of the oocyte in some homozygous female germline clones. A high density of microtubules is detected throughout the oocyte in these germline clones.

l(2)gl1/l(2)gl4 larval brain neuroblasts show overproliferation.

l(2)gl4/Df(2L)net62 mutant larvae have an extended third instar period during which the brain and imaginal discs undergo neoplastic growth.

When brain fragments from 10 day old l(2)gl4/Df(2L)net62 mutant larvae are transplanted into adult hosts and incubated for 12 days the cells proliferate extensively and fill the host abdomen. l(2)gl4/Df(2L)net62 tumours are able to pass through the muscle layer and form micrometastases. Cells are also able to pass through the basement membranes that surround the muscle layer of epithelial sheath, indicating that the tumour cells are able to completely pass through all three layers of the epithelial sheath. Each micrometastasis develops in the haemolymph filled space between the epithelial sheath and the basement membrane surrounding the follicular epithelium.

When transplanted into wild-type, l(2)gl4/Df(2L)net62 tumor cells form micrometastases in 15.8% of ovarioles after 12 days of proliferation. All of the flies examined exhibit at least one ovariole with a micrometastasis.

After transplantation of l(2)gl4/Df(2L)net62 brain tissue into ovoD1 hosts for 7 days then retransplanting into wild-type hosts for 12 days, micrometastases form in 23.8% of the ovarioles analyzed. Further incubation time increases the rate of metastasis. l(2)gl4/Df(2L)net62 brain fragments that have been transplanted into ovoD1 hosts for 7 dys, then retransplanted into ovoD1 hosts for 7 days, and finally transplanted into wild-type hosts for 12 days form micrometastases in 41.3% of ovarioles. While the frequency of invasion increases significantly, the micrometastases that form in the hosts do not penetrate the follicular epithelium and appear similar in size at each time point.

Mutant embryos produce a continuous, malformed cuticle.

Mutant eye discs (generated using the eyFLP-cell lethal system) show disorganised cellular architecture and reduced differentiation compared to wild type.

Larvae containing mutant eye discs generated using the eyFLP-cell lethal system are increased in size compared to control larvae when examined as pupariation commences. The animals do not develop into adults.

Wing discs contain regions of neoplastic overgrowth in animals in which clones have been induced in the wing, haltere and leg discs (using the UbxFLP-cell lethal system). Eye discs are normal in these animals.

Clones of cells mutant for l(2)gl4 do not proliferate as well as wild-type cells but exhibit a cell polarity defect.

Flies containing homozygous clones generated using the EGUF system (this generates eye discs composed exclusively of homozygous tissue) are recovered as headless pharate adults.

Delamination and migration of border follicle cells are both accelerated in l(2)gl4 heterozygotes. In l(2)gl4/l(2)glts3 flies the border follicle cells have much reduced polarity. Delamination of these cells is delayed, but their migration is accelerated.

Homozygous mutant clones in the follicle cells leads to multilayered follicle cells. Mutant clones also cause a rough germline boundary and have invasive properties.

When l(2)gl4w3 clones are made on the notum, large tumours are seen along with disruptions of junctions between epithelial cells. Within these clones, external sensory organs appear malformed containing additional external cells. Most (84%) mutant external sensory organs consist of three sockets and one hair. Clusters of four sockets are also present at a lower (12%) frequency. Both internal cells are seen to be missing most (96%) of the time.

Misoriented spindles are sometimes observed the neuroblasts of l(2)gl4 embryos.

l(2)gl4 L3 larval neuroblasts are reduced in size compared to wild-type. l(2)gl4/l(2)gl334 L3 larval brains are larger in volume (65% larger) than l(2)gl334/+ brains.

When homozygous mutant larval brain tissue is transplanted into wild-type adult abdomens, the injected tissue proliferates as a primary tumour and invades adjacent tissue, and cells migrate away from the primary tumour to generate widespread metastatic colonies. Homozygous mutant brains are composed of overgrown tissues with loosely adherent cells.

Eye discs are reduced in size. When clones are induced in the wing with the result that the mutant patches affect both wing surfaces wing veins are lost. When the clone only covers one surface of the wing vein differentiation is unaffected. In either case, clones in intervein regions are wild type.

Clones of homozygous follicle cell undergo extra cell divisions after stage 6 which is accompanied by a loss of apical-basal polarity. The clones frequently lead to the formation of multiple layers of follicle cells.

Follicle cell clones homozygous for l(2)gl4 show loss of cell shape and monolayer organisation.

Salivary glands isolated from 8 day old third instar l(2)gl334/l(2)gl4 larvae and maintained in Schneider culture medium for 24 hours are considerably reduced in size compared to wild-type controls and have a "bunch of grapes" shape. The cells of the mutant glands are nearly spherical in form with a reduced surface of cell-to-cell contact. Administration of 10[-5]M 20-hydroxyecdysone fails to induce the histolysis of the mutant glands. No sign of vacuolisation or abnormal pattern of organelle distribution can be detected in treated mutant salivary gland cells and the overall organisation of the glands and structure of the cells is similar to those of untreated mutant glands.

Embryos derived from maternal homozygous germline clones show an early loss of embryonic epithelial apical/basal polarity and neuroblast defects. l(2)gl4 homozygous embryos show a decrease in EL neuron number at stage 17.

The size of the larval imaginal discs of homozygotes is much reduced if they are also homozygous for corto420.

The median survival of adult hosts transplanted with hemizygous l(2)gl4/Df(2L)net62 brain fragments is reduced compared to adult hosts transplanted with wild-type brain fragments. Cells from transplanted hemizygous brain fragments are highly metastatic in the wild-type hosts, forming at least one secondary tumour in 87% of cases. Imaginal discs from l(2)gl4/Df(2L)net62 larvae form secondary tumours in 43% of hosts.

Can be partially rescued, to produce a small proportion of viable adults, by l(2)glhs.PM. Such rescued female flies show small ovaries and fusion of the germarium to the youngest egg chambers.

Malpighian tubule colour: colourless. Larvae exhibit melanotic tumours of the imaginal discs and brain ganglia. l(2)gl4 Abl2 double mutants exhibit a deformed cephalopharyngeal skeleton.

l(2)gl4 mutant clones influence the stability of the anterior/posterior compartment boundary in the developing wing. Clones can straddle the boundary, and display loss of pattern due to cell death resulting in scalloping. Surrounding wild type cells show aberrant growth and differentiation. Wing size is reduced and cross veins are lost. Wild type wing can become folded. Some (less than 10%) clones are characterized by unstructured or poorly cuticularized areas, or clustering of mutant cells in vesicles.

Homozygous clones give rise to tumorous structures with disrupted cuticle patterns.

Larval period is extended. Brains increase in size throughout the extended larval period, and become progressively more abnormal in morphology, failing to remain as an intact tissue. When transplanted into wild-type adult hosts mutant brains can develop into enormous tumors.

The brain ganglia of 4 to 5 day old homozygous larvae appear smaller than those of 4 to 5 day old wild-type larvae, but are normal in shape. The size of the brain increases rapidly from day 6 onwards in homozygous larvae, and after day 8 appears disorganised and forms a large irregular mass. There are fewer replicating nuclei in the brain ganglia of homozygous larvae compared to the brain ganglia of wild-type larvae, up to day 5. 7 day old brain ganglia of homozygous larvae contain more replicating nuclei than the brain ganglia of wild-type 7 day old larvae. The distribution of the replicating nuclei is abnormal.

No eggs are produced by females containing homozygous germ-line clones.

Hemizygous larvae do not pupariate at 15 or 29oC.

The wing discs in homozygous larvae form large amorphous tissue masses, which are composed of disorganised sheets and cords of cells. The number of gap junctions is reduced in these discs.

Clones of mutant tissue grow and metamorphose nearly normally. Results show that the mutation acts autonomously in tissue transplants but non-autonomously in genetic mosaics within an imaginal disc.

Homozygous third instar larvae appear transparent and bloated. Pseudopupae are formed, but the animals die in the puparia. The third larval instar brain behaves as an invasive, transplantable lethal neuroblastoma and the imaginal discs develop into benign, transplantable and lethal neoplasms. The cells grow rapidly in a disorganised way when transplanted into adult female hosts. Ultrastructural studies show that the disc cells do not form tight junctions with each other, in contrast to wild-type. The lymph gland is also abnormal; in most cases the single lobes are much enlarged and fused, and contain a large number of fairly undifferentiated round cells which are released into the body cavity and invade the imaginal discs.

extreme allele: larval brain and optic lobes become enlarged and disorganized and the imaginal discs large and clumped; when discs of larvae are transplanted into wild-type-female abdomens, they form large contained tumors, whereas transplanted optic primordia from larval brains form invasive neuroblastomas, which grow rapidly, killing the host within 7-14 days; they can be serially cultured in adult abdomens. lethal phase: larvae 89.1%, pupae 10.9%

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

Ras85DV12.UAS, Scer\GAL4GMR.PF, l(2)gl4 has neoplasia phenotype, suppressible by Uev1A[+]/Uev1ADG14805

l(2)gl4 has neoplasia phenotype, suppressible by Sema5c23-2

l(2)gl4 has neoplasia phenotype, suppressible by pnt115-1

NOT suppressed by
Enhancer of
NOT Enhancer of
Statement
Reference

l(2)gl4 is a non-enhancer of visible phenotype of upd1GMR.PB

Suppressor of
NOT Suppressor of
Statement
Reference

l(2)gl4 is a non-suppressor of visible phenotype of upd1GMR.PB

Other
Statement
Reference

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

Phenotype Manifest In
Enhanced by
NOT Enhanced by
Suppressed by
Statement
Reference

Ras85DV12.UAS, Scer\GAL4GMR.PF, l(2)gl4 has larva phenotype, suppressible by Uev1A[+]/Uev1ADG14805

l(2)gl4 has phenotype, suppressible by apt97-2

l(2)gl4 has phenotype, suppressible by Dpse\l(2)gl+t12.2

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

l(2)gl4 is a non-suppressor of eye phenotype of upd1GMR.PB

Other
Statement
Reference

Fmr13, l(2)gl[+]/l(2)gl4 has synapse & larval neuromuscular junction phenotype

Fmr13/Fmr1[+], l(2)gl4 has synapse & larval neuromuscular junction phenotype

capt10, l(2)gl4 has follicle cell & actin filament | somatic clone phenotype

Additional Comments
Genetic Interactions
Statement
Reference

In pupal dorsal thorax epithelium clones that are homozygous for l(2)gl4 and simultaneously express show CG7379GD12222 under the control of Scer\GAL4pnr.PU, pre-invasive cells show increased apoptosis.

Double cyst1, l(2)gl4 maternal-zygotic mutants show embryonic cuticle defects that are similar to those observed in l(2)gl4 single maternal-zygotic mutants (i.e. head or head cuticle morphogenesis), and milder than those observed in cyst1 single maternal-zygotic mutants.

Whole-eye disc clones both l(2)gl4 homozygous and expressing Ras85DV12.cUa.UAS under the control of Scer\GAL4Act5C.PP form tumors that invade into the VNC; the VNC invasion phenotype is nearly suppressed by the co-expression of pucUAS.cUa, partially suppressed by the co-expression of licJF01433 and partially suppressed by licG0252 heterozygosity; however, the size of the primary tumor is not affected by these manipulations.

Whole eye-antennal disc clones that both express Ras85DV12.UAS under the control of Scer\GAL4Act.PU and are homozygous for l(2)gl4 form large tumors that invade the adjacent ventral nerve cord by day 7 after egg laying; individuals have an extended larval stage and die as bloated 3rd instar larvae.

Scer\GAL4Scer\FRT.Act5C>Ras85DV12.Scer\UAS;l(2)gl4/l(2)gl4 are also highly tumorigenic and have invasive capability and their overgrowth as well as invasiveness is significantly suppressed by co-expression of either fmtScer\UAS.cMa or PpVScer\UAS.P\T.N.T:Avic\GFP-EGFP and to even greater extent when both transgenes are expressed simultaneously in the mutant clones (however this effect is not due to increase in cell death).

Expression of PfkHMS01324 suppresses the tumorigenic overgrowth seen in l(2)gl4 mutant wing discs expressing ykiScer\UAS.cOa.T:SV5\V5 under the control of Scer\GAL4tub.PU.

l(2)gl4 mutant wing disc clones expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4tub.PU show increased levels of hypoxia compared to controls or either mutant alone. Ectopic tracheal structures are seen at the basal side of the disc, and in some cases several branches depart from a central mass and enclose a rudimentary lumen. l(2)gl4 Ras85DV12.Scer\UAS cells form mosaic tracheal branches with resident tracheal cells. Clone cells at the apical side of the disc are frequently interconnected with clone cells at the basal side by a bridge of tumour cells.

When l(2)gl4 mutant clones expressing Ras85DV12.Scer\UAS are generated at 48 hours after egg laying (AEL) using a tracheal specific driver (Scer\GAL4btl.PU) no wing disc clones are observed. Tracheal clones are generated when clones are induced at 0-4 hours AEL but no overgrowth is observed.

No significant increase in the proportion of hemisegments with abnormal number of neurons in the asymmetrically dividing RP2 neural lineage is is observed in wtsx1/+;l(2)gl4/+ double heterozygous embryos compared to either of the single heterozygotes or wild type.

Expression of Ras85DV12.Scer\UAS under the control of Scer\GAL4Scer\FRT.Act5C in l(2)gl4 mutant cells in eye-antennal discs using the ey-FLP/MARCM system results in tumor-like growth with invasive migration into the ventral nerve cord of the CNS. The growth and invasion of these tumors is dramatically suppressed upon co-expression of pucScer\UAS.cMa.

Expression of benGD1387 significantly suppresses the growth and invasion of the tumors seen when Ras85DV12.Scer\UAS is expressed in l(2)gl4 mutant cells in eye-antennal discs using the ey-FLP/MARCM system.

One copy of ben1 partially suppresses the growth and invasion of the tumors seen when Ras85DV12.Scer\UAS is expressed in l(2)gl4 mutant cells in eye-antennal discs using the ey-FLP/MARCM system.

HrsD28 Stam2L2896 l(2)gl4 follicular epithelium clones display normal epithelial morphology.

The brains of l(2)gl4 clu169 double mutant flies are similar in size to wild type.

park1 suppresses the enlarged brain phenotype seen in l(2)gl1/l(2)gl4 mutant third instar larvae.

l(2)gl4 mutant clones in a Df(3L)H99/+ mutant background display neoplastic transformation in the proximal domain of the wing disc. Distal clones initially survive but are extruded from the epithelium after day five. Distal neoplasia does occur when clones are generated in a minute/+ background to alleviate cell competition, but the onset of transformation is substantially delayed.

ft8 l(2)gl4 double mutant clones in the proximal domain of the wing disc exhibit overproliferation and neoplastic transformation. Clones in the distal domain are eliminated.

Expression of dshScer\UAS.cNa under the control of Scer\GAL4tub.PU in l(2)gl4 mutant wing disc mutant clones results in overproliferation and neoplastic transformation in the proximal domain. Clones in the distal domain are eliminated, even when the growth temperature is elevated.

Expression of tkvQ253D.Scer\UAS.cNb under the control of Scer\GAL4tub.PU in l(2)gl4 mutant wing disc mutant clones results in overproliferation and neoplastic transformation in the proximal domain. Clones in the distal domain are eliminated, even when the growth temperature is elevated.

Expression of btl::EgfrScer\UAS.T:λ\cI-DD under the control of Scer\GAL4tub.PU in l(2)gl4 mutant wing disc mutant clones results in overproliferation and neoplastic transformation in the proximal domain. Clones in the distal domain are eliminated. However at an elevated growth temperature (29[o]C) distal neoplasia is also seen.

Expression of ykiScer\UAS.cHa under the control of Scer\GAL4tub.PU in l(2)gl4 mutant wing disc mutant clones results in overproliferation and neoplastic transformation in both the proximal and distal domains, although the onset of neoplasia is delayed in distal cells compared to proximal cells.

Distal wing disc clones expressing vgScer\UAS.cKa under the control of Scer\GAL4tub.PU in a l(2)gl4 mutant background show rapid elimination and are rarely recovered. Proximal clones are more often recovered but also undergo cell death and basal extrusion. No neoplastic transformation is seen.

Expression of ykiScer\UAS.cHa does not suppress the poor recovery rate of distal wing clones expressing vgScer\UAS.cKa under the control of Scer\GAL4tub.PU in a l(2)gl4 mutant background. Extensive cell death is still seen. Survival of proximal clones is somewhat improved, but unlike in l(2)gl4 mutant clones alone, neoplastic transformation is still not observed until day four of clone induction and the clones display dense cell packing and compact nuclear morphology.

Expression of hthScer\UAS.T:Avic\GFP under the control of Scer\GAL4tub.PU in l(2)gl4 mutant wing disc mutant clones results in overproliferation and neoplastic transformation in the proximal domain. Clones in the distal domain are mostly eliminated.

Expression of hthHMS01112 does not suppress the overproliferation and neoplastic transformation seen in both the proximal and distal wing disc domains when ykiScer\UAS.cHa is expressed under the control of Scer\GAL4tub.PU in l(2)gl4 mutant clones.

Expression of Ras85DV12.Scer\UAS under the control of Scer\GAL4tub.PU in l(2)gl4 mutant wing disc mutant clones results in overproliferation and neoplastic transformation in both the proximal and distal domains.

Expression of hthScer\UAS.T:Avic\GFP under the control of Scer\GAL4tub.PU induces neoplastic transformation in l(2)gl4 mutant eye disc clones.

Expression of Ras85DV12.Scer\UAS in l(2)gl4 mutant cells in eye-antenna discs using the ey-FLP/MARCM system induces strong tumour-like growths, with invasive migration into the VNC 8 days after egg laying. Such animals keep growing as oversized larvae carrying huge tumours in their heads and die before pupation.

Blocking JNK signaling by expression of pucScer\UAS.cMa dramatically suppresses the growth and invasion behaviours of Ras85DV12.Scer\UAS/l(2)gl4 tumours.

Loss of Src42A, through expression of Src42ANIG.7873R, dramatically suppresses tumour cell invasion into the ventral nerve cord found in Ras85DV12.Scer\UAS/l(2)gl4 mutants and enables the animals to survive to the pupal stage, whereas the tumour size remains largely unaffected.

Loss of Src64B, through expression of Src64BGD12263, dramatically suppresses tumour cell invasion into the ventral nerve cord in Ras85DV12.Scer\UAS/l(2)gl4 mutants and enables the animals to survive to the pupal stage, whereas the tumour size remains largely unaffected.

Expression of Ras85DV12.Scer\UAS in l(2)gl4 mutant developing eye-antennal discs, under the control of Scer\GAL4GMR.PF, results in tumour-like overgrowths, with invasive migration into the ventral nerve cord of the central nervous system. The mutant animals keep growing as oversized larvae with huge tumours in the head region and die before pupation.

Inactivation of JNK signaling, through the expression of pucScer\UAS.cMa, dramatically suppresses the Ras85DV12.Scer\UAS/l(2)gl4 mutant tumour growth and invasion, and rescues animals to pupal stage.

Expression of Uev1AGD6650 mutant background dramatically suppresses the Ras85DV12.Scer\UAS/l(2)gl4 mutant tumour growth and invasion, and rescues animals to pupal stage.

A Uev1ADG14805 heterozygous mutant background dramatically suppresses the Ras85DV12.Scer\UAS/l(2)gl4 mutant tumour growth and invasion, and rescues animals to pupal stage.

Expression of MycScer\UAS.T:Ivir\HA1 under the control of Scer\GAL4tub.PU suppresses the reduction in l(2)gl4 mutant wing disc clone size compared with controls. The clones are round in shape and massively overgrown, with the largest clones located in the proximal regions of the disc (the hinge and pleura). Cells in these clones are larger than in l(2)gl4 clones, but this gain in cell size only accounts for a small fraction of clone expansion. The majority of the large clones show little or no apoptosis, but some apoptosis is seen in smaller clones and just outside of the overgrown clones. The cells exhibit defects in apical-basal polarity. There is some discontinuity across the basement membrane, suggesting the cells have invasive properties.

Wing pouch clones expressing bskDN.Scer\UAS under the control of Scer\GAL4tub.PU in a l(2)gl4 mutant background do not show increased apoptosis, but are smaller in size than wild type controls. In contrast, clones in the proximal regions of the wing disc lose polarity and overgrow.

Expression of egrGD12658 under the control of Scer\GAL4tub.PU does not affect the reduction in l(2)gl4 mutant wing disc clone size compared with controls.

Expression of MycGD1419 under the control of Scer\GAL4tub.PU suppresses the cell polarity defects seen in l(2)gl4 mutant wing disc clones generated in a Minute background, even when the mutant clone tissue occupies a larger proportion of the disc. No degradation of the basement membrane occurs and clones do not form tumorous masses, either in the wing pouch or proximal (hinge and pleura) regions.

Expression of Pi3K92EScer\UAS.T:Hsap\MYC,T:Hsap\CAAX under the control of Scer\GAL4tub.PU does not suppress the defective growth seen in l(2)gl4 mutant clone cells.

dsh3 maternal/l(2)gl4 zygotic double mutants display a cuticle which resembles the l(2)gl4 maternal mutant phenotype. Patches of denticles are observed which lack proper alignment, and the ventral epithelium is continuous and formed. Denticle precursors are not properly oriented toward the posterior of cells and denticle placement appears to be random within each cell.

The cuticle defects observed when bazS980A.Scer\UAS.T:Avic\GFP is expressed under the control of Scer\GAL4arm.PS are strongly suppressed in a l(2)gl4 mutant background.

Expression of pucScer\UAS.cMa under the control of Scer\GAL4tub.PU strongly suppresses the apoptosis that is seen in l(2)gl4 clones in the wing disc. Basal extrusion of mutant cells is not fully blocked in these discs.

Expression of mahjScer\UAS.P\T.cTa under the control of Scer\GAL4tub.PU strongly suppresses both apoptosis and basal extrusion of l(2)gl4 clones in the wing disc.

Embryos double mutant for arm043A01 both maternally and zygotically and l(2)gl4 zygotically display abnormal embryonic cuticle.

Embryos double mutant for arm2 both maternally and zygotically and l(2)gl4 zygotically display a cuticle phenotype similar to that of l(2)gl4 single mutants.

Embryos triple mutant for sggM11 both maternally and zygotically and arm2 both maternally and zygotically and l(2)gl4 zygotically show a cuticle phenotype that is similar to that of zygotic l(2)gl4 single mutants.

Cuticles of embryos double mutant for armF1α maternally and zygotically and l(2)gl4 zygotically resemble armF1α single mutant embryos.

Embryos triple mutant for sggM11 both maternally and zygotically and armF1α both maternally and zygotically and l(2)gl4 zygotically show a cuticle phenotype that is similar to that of zygotic l(2)gl4 single mutants.

Cuticles of embryos double mutant for sggM11 both maternally and zygotically and l(2)gl4 zygotically resemble that of l(2)gl4 single mutants.

The addition of one copy of mts02496 or mtsXE-2258 to l(2)gl4/l(2)glts3 flies reduces the eclosion rate to 72% and 42% respectively.

The presence of one copy of mts02496 or mtsXE-2258 in l(2)gl4/l(2)glts3 flies increases the frequency of defective bristle formation to 33% and 64% respectively (compared to 28% in l(2)gl4/l(2)glts3 mutants).

The overproliferation of larval brain neuroblasts seen in l(2)gl1/l(2)gl4 animals is enhanced by expression of bazScer\UAS.P\T.T:Avic\GFP under the control of Scer\GAL41407.

The overproliferation of larval brain neuroblasts seen in l(2)gl1/l(2)gl4 animals is completely suppressed by expression of bazGD1384 under the control of Scer\GAL41407.

The overproliferation of larval brain neuroblasts seen in l(2)gl1/l(2)gl4 animals is enhanced by numb15/+ and is weakly suppressed by numbS52F/+.

The cuticle defects seen at 25[o]C in embryos derived from exo84onr/Df(3R)Espl3 females mated to exo84onr heterozygous males are suppressed by l(2)gl4.

Expression of Traf6dsRNA.Scer\UAS (under the control of Scer\GAL4Act5C.PI) using the FLP/FRT system strongly suppresses metastatic behaviour in l(2)gl4 mutants expressing Ras85DV12.Scer\UAS.

Expression of Traf4dsRNA.Scer\UAS (under the control of Scer\GAL4Act5C.PI) using the FLP/FRT system fails to suppress metastatic behaviour in l(2)gl4 mutants expressing Ras85DV12.Scer\UAS.

Expression of Tak1dsRNA.Scer\UAS (under the control of Scer\GAL4Act5C.PI) using the FLP/FRT system strongly suppresses metastatic behaviour in l(2)gl4 mutants expressing Ras85DV12.Scer\UAS.

Expression of hepdsRNA.Scer\UAS (under the control of Scer\GAL4Act5C.PI) using the FLP/FRT system strongly suppresses metastatic behaviour in l(2)gl4 mutants expressing Ras85DV12.Scer\UAS.

Expression of wgndsRNA.Scer\UAS (under the control of Scer\GAL4Act5C.PI) using the FLP/FRT system partially suppresses metastatic behaviour in l(2)gl4 mutants expressing Ras85DV12.Scer\UAS.

Expression of PvrdsRNA.Scer\UAS (under the control of Scer\GAL4Act5C.PI) using the FLP/FRT system does not suppress metastatic behaviour in l(2)gl4 mutants expressing Ras85DV12.Scer\UAS.

Fmr13/+; l(2)gl4/+ larvae exhibit hyperplasia of neuromuscular junctions: The number of boutons per neuromuscular juntion is significantly increased.

Marked clones in the eye disc expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C.PI and which are also homozygous for l(2)gl4 show metastatic behaviour.

The reduced size seen in l(2)gl4 L3 larval neuroblasts is not suppressed by aPKCk06403/aPKCk06403 and may in fact be slightly enhanced. The increase in L3 larval brain volume seen in l(2)gl334/l(2)gl4 animals is partially suppressed by aPKCk06403/+. aPKCk06403 heterozygosity cannot suppress the l(2)gl4 "small neuroblast" phenotype.

l(2)gl4 shows marked rescue of the crb2 phenotype, as the majority of the cuticle is restored in the double mutant embryos. Formation of the zonula adherens is largely rescued in crb2 ; l(2)gl4 double mutant embryos.

When mutant larval brain tissue is transplanted from animals homozygous for l(2)gl4 and also homozygous for apt97-2, tumorigenesis is still seen, but the metastasis seen in tissue from l(2)gl4 animals alone is not seen. When mutant larval brain tissue is transplanted from animals homozygous for l(2)gl4 and also homozygous for Sema-5c23-2, a suppression of the normal tumorigenesis and metastasis phenotypes is seen. When mutant larval brain tissue is transplanted from animals homozygous for l(2)gl4 and also homozygous for pnt115-1, the lethality of injected tumours is accelerated. The addition of Sema-5c23-2 to l(2)gl4 larvae has no gross effect on the larval brain pehnotype.

F-actin is often seen accumulating at a single, randomly positioned site within the cell in capt10 l(2)gl4 double mutant follicle cell clones.

Xenogenetic Interactions
Statement
Reference

Expression of BacA\p35Scer\UAS.cHa under the control of Scer\GAL4tub.PU strongly suppresses the apoptosis that is seen in l(2)gl4 clones in the wing disc. Basal extrusion of mutant cells is not fully blocked in these discs.

Flies containing homozygous l(2)gl4 clones generated using the EGUF system (this generates eye discs composed exclusively of homozygous tissue) which are also expressing Hsap\LLGL1Scer\UAS.cGa under the control of Scer\GAL4ey.PH are recovered as pharate adults but they show a partial eversion of the head with the development of rudimentary eyes.

l(2)gl4 homozygotes that are expressing Hsap\LLGL1Scer\UAS.cGa under the control of Scer\GAL4Act5C.PU either eclose into viable adults (46%) or are recovered as completely developed pharate adults.

Mutant phenotype completely rescued by Dpse\l(2)gl+t12.2.

Complementation and Rescue Data
Fails to complement
Comments

Expression of Scer\GAL4hh.PU>l(2)glScer\UAS.P\T.T:Avic\GFP rescues the cell polarity defects in l(2)gl4/l(2)gl334 mutants.

Expression of Scer\GAL4hh.PU>l(2)glASA.Scer\UAS.T:Avic\GFP rescues the cell polarity defects in l(2)gl4/l(2)gl334 mutants and l(2)gl4 mutant somatic clones, but reveals spindle orientation defects.

Expression of Scer\GAL4hh.PU>l(2)glScer\UAS.T:Uuuu\Myr-Unk rescues the cell polarity defects in l(2)gl4/l(2)gl334 mutants and l(2)gl4 mutant somatic clones, but reveals spindle orientation defects.

52% of l(2)gl4 homozygotes that are expressing l(2)glScer\UAS.cOa under the control of Scer\GAL4Act5C.PU eclose into viable adults.

Images (0)
Mutant
Wild-type
Stocks (3)
Notes on Origin
Discoverer

Gateff.

Comments
Comments

Germ-line clonal analysis indicates that the l(2)gl product is required in the germ-line for egg development. Analysis of follicle cell mosaics indicates that l(2)gl function is required in the follicle cells.

Homozygous l(2)gl4 tissue behaves autonomously in transplantation experiments.

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (8)
Reported As
Symbol Synonym
lgl4
(Lacin et al., 2024, Wang et al., 2024, Bharti et al., 2023, Chatterjee et al., 2023, Fangninou et al., 2023, Tian et al., 2023, Chatterjee et al., 2022, Ding et al., 2022, Liu et al., 2022, Singh et al., 2022, Yang et al., 2022, Fic et al., 2021, Ito and Igaki, 2021, Rusu et al., 2021, Wu et al., 2021, Bajpai et al., 2020, Biehler et al., 2020, Canales Coutiño et al., 2020, Guo et al., 2020, Domingos et al., 2019, Mishra-Gorur et al., 2019, Moreira et al., 2019, Silver et al., 2019, Sun et al., 2019, Zhang et al., 2019, Chen et al., 2018, Ma et al., 2017, Sallé et al., 2017, Bergstralh et al., 2016, Kim et al., 2016, Bell et al., 2015, Besson et al., 2015, de Vreede et al., 2014, Goh et al., 2013, Khan et al., 2013, Ma et al., 2013, Ma et al., 2013, Izumi et al., 2012, Bahri et al., 2010, Doerflinger et al., 2010, Froldi et al., 2010, Janic et al., 2010, Kaplan and Tolwinski, 2010, Krahn et al., 2010, Tamori et al., 2010, Tong et al., 2010, Zeng et al., 2010, Huang et al., 2009, Kaplan et al., 2009, Mao and Freeman, 2009, Ogawa et al., 2009, Rhiner et al., 2009, Roegiers et al., 2009, Tian and Deng, 2008, Vaccari et al., 2008, Wirtz-Peitz et al., 2008, Wirtz-Peitz et al., 2008, Beaucher et al., 2007, Blankenship et al., 2007, Menut et al., 2007, Slack et al., 2007, Tyler et al., 2007, Betschinger et al., 2006, Igaki et al., 2006, Igaki et al., 2006, Langevin et al., 2005, Roegiers et al., 2005, Brumby et al., 2004, Trunova and Shearn, 2004, Abdelilah-Seyfried et al., 2003, Albertson and Doe, 2003, Bach et al., 2003, Bilder et al., 2003, Grifoni et al., 2003, Justice et al., 2003, Pagliarini and Xu, 2003, Petritsch et al., 2003, Rolls et al., 2003, Tanentzapf and Tepass, 2003, Woodhouse et al., 2003, Arquier et al., 2001, Deng et al., 2001, Bilder et al., 2000, Ohshiro et al., 2000, Peng et al., 2000, Woodhouse et al., 1998, Saha and Sinha, 1996)
Name Synonyms
Secondary FlyBase IDs
    References (131)