Open Close
General Information
Symbol
Dmel\Lar5.5
Species
D. melanogaster
Name
FlyBase ID
FBal0048849
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
Dlar5.5
Key Links
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Nucleotide change:

G19717177A

Reported nucleotide change:

G1773A

Amino acid change:

W552term | Lar-PA; W534term | Lar-PB; W534term | Lar-PD; W557term | Lar-PF; W557term | Lar-PG; W549term | Lar-PH; W563term | Lar-PI

Reported amino acid change:

W?term

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

Protein truncated in FnII domain 3.

Nucleotide substitution: G1773A. (Coordinates refer to cDNA sequence). The substitution causes a W to be replaced by a TGA stop codon, resulting a a protein truncated in the extracellular 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

actin filament & follicle cell | somatic clone | cell non-autonomous

anterior fascicle & axon | ectopic (with Lar13.2)

photoreceptor cell R7 & axon (with Lar2127)

photoreceptor cell R7 & growth cone (with Lar2127)

Detailed Description
Statement
Reference

Lar5.5/Lar13.2 mutant follicle cells in mosaic egg chambers exhibit a reduction in actin-rich protrusions along the membrane as compared to controls, but only in egg chambers that are completely mutant or in large mutant clones. No defects in global alignment of contractile actin bundles are seen in these egg chambers.

Eggs from Lar5.5/Lar13.2 mutant egg chambers are moderately rounded as compared to wild type.

Lar5.5 homozygous mutant embryos exhibit ISNb bypass phenotypes in 31% of hemisegments.

Lar5.5 heterozygous embryos do not exhibit ISNb guidance defects.

Lar5.5/Lar13.2 larvae show a reduction in bouton number at the neuromuscular junction compared to wild type.

28% of Lar13.2/Lar5.5 mutants display a motor axon guidance phenotype known as "ISNb bypass" in which ISNb axons successfully split away from the ISN pathway at the exit junction, but can fail to grow into the muscle field at their normal entry point. Instead, such axons travel along parallel to the ISN, underneath the muscles, until they reach the dorsal edge of the VLM field.

Carefully nurtured Lar5.5/Lar13.2 escapers of the lethality can be raised to adulthood. Stage 14 oocytes produced by these adults are abnormally round.

Homozygous and heterozygous larvae have fewer boutons (both type Ib and type Is) at the muscle 6/7 neuromuscular junction than wild type. Overall neuromuscular junction (NMJ) ultrastructure looks normal in homozygous larvae, but 61% of individual active zones are larger than the largest active zones found in wild-type NMJs and the mean total area of the mutant active zones is 2.5-fold greater than wild type.

In Lar5.5/Lar13.2 mutants, some oocytes fail to elongate significantly. This phenotype is moderate in penetrance (14.1% defective stage 14 oocytes). No defects are seen in major aspects of oocyte patterning; both the micropyle and the dorsal appendages are formed in their correct positions, although the latter are often shortened relative to those of the wild-type. Similarly the oocyte nucleus is correctly positioned in the dorsal-anterior compartment in rounded oocytes. In Lar5.5 somatic clones in the follicle cells, defects are seen in cytoskeletal organisation. In cases where disruption in F-actin are evident, defects are always observed in both mutant cells and in wild-type cells surrounding the clone. Although global organisation of actin polarity is lost around these clones, actin filaments tend to be similarly polarised in adjacent cells.

Actin polarisation in Lar5.5 germ-line clones is almost completely normal. However, egg chambers that contain somatic clones of mutant follicle cells display severely abnormal actin polarisation. These defects affect both mutant and wild-type cells. The genotype od the polar cells is not a determinant - cases of mutant polarisation surrounding wild-type polar cells are seen, the inverse (mutant polar cells surrounded by wild-type polarisation) is also seen. In mutant germline clones, region 2b cysts never fail to become lens-shaped and never contain more than one round of follicle in the process of budding. By contrast, when most of the follicle cells in region 2b and 3 are mutant (a relatively rare phenotype) then 62% of the germaria contain such defects.

R7 growth cones extend beyond the R8 termini in Lar2127/Lar5.5 animals 15 hours after pupariation as occurs in wild type, although the R7 growth cones have a compact, club-like shape instead of the normal expanded morphology. Only 52.9% of Lar2127/Lar5.5 R7 axons select their correct target layer.

Lar5.5/Lar13.2 transheterozygous embryos have a parallel bypass phenotype in the ISNb nerve.

Homozygotes show an ISNb bypass phenotype at moderate frequency.

ISNb axons often show a "bypass" phenotype (failing to enter the normal muscle target domain just outside the ventral nerve cord and instead following the intersegmental nerve towards dorsal targets) in Larbypass/Lar5.5 embryos.

Truncation phenotypes of the ISN. Most ISNs reach PT1 (persistent twi cell 1) but have small terminal arbors. Combining Ptp69D or Ptp99A mutants increases the penetrance and severity of the ISN defects, the ISN pathway is truncated at specific branchpoint positions. Triple mutants lacking Lar, Ptp69D or Ptp99A exhibit much stronger ISN phenotypes than any single or double mutant. Mutation affects SNb guidance and synaptogenesis within the VLM (ventrolateral muscle) field, a parallel bypass phenotype is observed (SNb axons grow alongside the ISN). SNbs fail to form the normal pattern of synaptic branches and exhibit navigation errors at the muscle field entry point. Growth alongside the ISN is likely to be due to inappropriately active Ptp99A rather than a failure of Lar-mediated VLM recognition. Lar, Ptp69D or Ptp99A triple mutants also exhibit fusion bypass phenotype of the SNb axons. Fusion bypass is seldom observed in any genotype in which Ptp69D is wild type. Removal of Ptp99A or Lar produces a 10- to 20- fold increase in the frequency of fusion bypass and an increase in complete stall phenotypes.

Approximately half of the homozygotes die as late instar larvae, and the remainder die attempting to eclose. A striking number of mutant larvae initiate pupation in the food. Mature pupae struggle to eclose and die part way out of the pupal case. Mutant embryos show defects in SNb and SNd motor axon guidance (full and partial bypass phenotypes) and to a lesser extent in the CNS (thinning of the most lateral longitudinal fascicle). The penetrance of these defects in not 100%. The embryonic lethality of Lar5.5/Lar13.2 is overcome by LarScer\UAS.cKa driven by Scer\GAL4elav-C155.

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

Lar5.5/Lar13.2 has egg | maternal effect phenotype, enhanceable | maternal effect by Abi[+]/AbiΔ20

Lar5.5/Lar13.2 has anterior fascicle & axon | ectopic phenotype, enhanceable by Sdc48/Sdc10608

Lar5.5/Lar13.2 has oocyte phenotype, enhanceable by mys1/mys[+]

Lar5.5/Lar13.2 has oocyte phenotype, enhanceable by mys10/mys[+]

Lar5.5/Lar2127 has photoreceptor cell R7 & axon phenotype, enhanceable by ena[+]/enaGC1

Lar5.5/Lar2127 has photoreceptor cell R7 & axon phenotype, enhanceable by trio1/trio[+]

Lar5.5 has phenotype, enhanceable by trioS137203/trio[+]

Suppressed by
Statement
Reference

Lar5.5/Lar2127 has photoreceptor cell R7 & axon phenotype, suppressible by trioGMR.PN

Enhancer of
Statement
Reference
Suppressor of
Other
Statement
Reference
Additional Comments
Genetic Interactions
Statement
Reference

AbiΔ20/+ strongly enhances the rounded egg phenotype of Lar5.5/Lar13.2 mutants.

Lar5.5 cknK.Δ324-331 double mutants exhibit an increase in frequency of the ISNb bypass phenotype from 31% in Lar5.5 single mutants to 49% in double mutants.

Lar5.5 cknK.Δ324-331 double heterozygous embryos display bypass phenotypes with 39% penetrance.

Lar5.5/+ enhances the reduction in bouton number at the neuromuscular junction which is seen in SdcKG06163/Df(2R)48 larvae (carrying SaraUbi.PJ to provide Sara function).

Sdc48/Sdc10608; Lar13.2/Lar5.5 mutants (in which Sara has been rescued by expression of the SaraUbi.PJ transgene) display an increased penetrance of the bypass phenotype (43% vs. 28%) relative to the corresponding Lar13.2/Lar5.5 transheterozygote. When SdcScer\UAS.cJa is expressed, under the control of Scer\GAL4how-24B, in a Lar13.2/Lar5.5 background, the SNa bifurcation phenotype seen when the transgene is expressed in a wild-type background is suppressed.

The addition of mys10/+ or mys1/+ to Lar5.5/Lar13.2 increases the penetrance of the oocyte elongation phenotype from 14.1% to 48.7% and about 40% respectively.

Lar5.5/Lar13.2 Ptp69D1 Ptp99A1/Df(3R)Ptp99AR3 triple mutant embryos show severe motor axon defects. The two inner bundles of the ventral nerve cord are very similar to that of wild-type, but the outer bundle, which develops later, is often discontinuous in late stage 16 triple mutant embryos. In addition, about one third of the ISNb nerves fail to leave the intersegmental nerve at the exit junction and continue to grow out along the common intersegmental nerve pathway in these triple mutant embryos. In most of these bypass hemisegments, only one intersegmental nerve branch is visible, and it is usually thicker than normal.

In Ptp10D1 Lar5.5/Lar13.2 Ptp99A1/Df(3R)Ptp99AR3 triple mutant embryos the two inner bundles of the ventral nerve cord are very similar to that of wild-type, but the outer bundle, which develops later, is often discontinuous.

The Ptp10D1 Lar5.5/Lar13.2 Ptp69D1 triple mutant embryonic phenotype involves ectopic midline crossing and longitudinal bundle fusion by the ventral nerve cord. The axons that abnormally cross the midline in the triple mutant embryos often grow diagonally to the other side without respecting the normal borders of the anterior and posterior commissures. In many cases, all of the connective axons appear to be rerouted across the midline, producing complete connective breaks.

Most of the ventral nerve cord axons abnormally cross the midline and the longitudinal bundles are almost absent in Ptp10D1 Lar5.5/Lar13.2 Ptp69D1 Ptp99A1/Df(3R)Ptp99AR3 quadruple mutant embryos. The longitudinal tracts are depleted of axons and the commissures are completely fused and much thicker than normal. No axons are ever observed to enter the ventrolateral muscle field in the quadruple mutant embryos.

In Ptp10D1 Lar5.5/Lar13.2 double mutant embryos, the normal SNa bifurcation is not observed in some hemisegments. This phenotype is only observed at low frequency.

Approximately half of the SNa nerves fail to bifurcate in Ptp10D1 Lar5.5/Lar13.2 Ptp69D1 triple mutant embryos.

Approximately half of the SNa nerves fail to bifurcate in Ptp10D1 Lar5.5/Lar13.2 Ptp99A1/Df(3R)Ptp99AR3 triple mutant embryos.

Approximately half of the SNa nerves either do not reach the bifurcation point at all or are very thin and wandering in Ptp10D1 Lar5.5/Lar13.2 Ptp69D1 Ptp99A1/Df(3R)Ptp99AR3 quadruple mutant embryos.

Approximately half of the intersegmental nerves terminate at the second lateral branch position in Ptp10D1 Lar5.5/Lar13.2 double mutant embryos. The remainder of the intersegmental nerves either terminate between the second lateral branch and the terminal arbor or make an abnormally small terminal arbor in these double mutant embryos.

Approximately half of the intersegmental nerves terminate at the first lateral branch point position and most of the remainder stop at the second lateral branch point in Lar5.5/Lar13.2 Ptp69D1 Ptp99A1/Df(3R)Ptp99AR3 triple mutant embryos.

Only about 15% of the intersegmental nerves terminate at the first lateral branch point position and most of the remainder stop at the second lateral branch point in Ptp10D1 Lar5.5/Lar13.2 Ptp69D1 Ptp99A1/Df(3R)Ptp99AR3 quadruple mutant embryos.

Ptp10D1; Lar13.2/Lar5.5; Ptp69D1 Ptp99AR3/Ptp69D8ex25 Ptp99A1 quadruple mutants have severely disrupted longitudinal tracts and most axons cross the midline. The bundles that cross the midline do not respect the normal boundaries of the commissures and the anterior and posterior commissures appear fused. No central nervous system abnormalities (by Fas2 staining) are seen in Ptp10D1; Lar5.5/Lar13.2 double mutant embryos.

The Larbypass/Lar5.5 ISNb "bypass" phenotype is suppressed by Abl1.

Mutation causes synergy of the Scer\GAL4elav-C155, Rac1N17.Scer\UAS full ISNb bypass phenotype.

Xenogenetic Interactions
Statement
Reference
Complementation and Rescue Data
Partially rescued by
Comments

Expression of LarScer\UAS.cKa under the control of Scer\GAL4elav.PU rescues the reduction in bouton number at the neuromuscular junction seen in Lar5.5/Lar13.2 larvae, while expression under the control of Scer\GAL4how-24B does not rescue the mutant phenotype.

Expression of LarΔFn2-9.Scer\UAS under the control of Scer\GAL4elav.PU partially rescues the reduction in bouton number at the neuromuscular junction seen in Lar5.5/Lar13.2 larvae.

Expression of either LarCSX2.Scer\UAS or LarΔIg123.Scer\UAS under the control of Scer\GAL4elav.PU fails to rescue the reduction in bouton number at the neuromuscular junction seen in Lar5.5/Lar13.2 larvae.

Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (5)
References (22)