FB2024_03 , released June 25, 2024
Allele: Dmel\Lis-1G10.14
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General Information
Symbol
Dmel\Lis-1G10.14
Species
D. melanogaster
Name
FlyBase ID
FBal0101616
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
Lis1G10.14
Key Links
Genomic Maps

Allele class
Nature of the Allele
Allele class
Progenitor genotype
Cytology
Description

Amino acid replacement: R239term.

Nucleotide substitution: C903T.

Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Nucleotide change:

C16183023T

Reported nucleotide change:

C903T

Amino acid change:

R239term | Lis-1-PA; R239term | Lis-1-PB; R239term | Lis-1-PF; R239term | Lis-1-PG

Reported amino acid change:

R239term

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

Lis-1k11702/Lis-1G10.14 transheterozygotes show shorter and thinner giant fiber terminals and disrupted electrophysiological connection between giant fibers and TTMn (as shown by am increased latency and a severely decreased ability to follow stimuli), as compared to controls.

Terminal cells in Lis-1G10.14 mutant trachea have thin cytoplasmic branches that lack air filling. Seamless tubes do not extend into these branches, although acetylated microtubules often do.

Severe delays in border cell migration are seen in follicle cell clones in which several of the migratory border cells, but none of the polar cells, are mutant.

Only 17% of Ecol\lacZarm.PV-negative germline stem cells remain three weeks after Lis-1G10.14 clone induction, compared to 75-80% in wild-type clones. Apoptotic Lis-1G10.14 mutant germline stem cells are not found, indicating that Lis-1 is required for controlling germline stem cell self-renewal but not survival in the ovary.

Lis-1G10.14 mutant germline stem cells produce fewer germline cysts than control germline stem cells. The percentage of BrdU-positive Lis-1G10.14 mutant germline stem cells is similar or even higher than that of control germline stem cells. Lis-1G10.14 mutant germline stem cells exhibit a misoriented spindle more frequently than control germline stem cells.

Lis-1G10.14 heterozygous germaria have about one cystoblast, as in wild-type germaria.

Homozygous Lis-1G10.14 mutant neurons in the third instar larva display abnormal dendritic arborization.

Homozygous clones in the class IV ddaC dendritic arborization (da) neurons have dendrite arbors with abnormal size and patterning.

In contrast to wild type, centrosome separation is often incomplete at the onset of prometaphase in Lis-1G10.14/Lis-1k13209 2nd larval instar brain neuroblasts. Microtubules emanating from both spindle poles often develop a Y-shaped morphology during prometaphase in these mutant cells, presumably because of the close apposition of the centrosomes. These Y-shaped spindles generally "recover" to form seemingly bipolar arrays of kinetochore microtubules by late metaphase. However, microtubule organising centres (MTOCs) occasionally detach from spindles or two MTOCs appear to maintain attachment to the same side of a half-spindle. In a few cases, the mutant neuroblasts contain more than the normal two MTOCs. Curved spindles and unfocused spindle poles are also seen in the mutant neuroblasts at metaphase.

The length of the prometaphase/metaphase interval is dramatically lengthened in Lis-1G10.14/Lis-1k13209 neuroblasts compared to wild type (average of 46 minutes 54 seconds +/- 18 minutes 33 seconds compared to 6 minutes 12 seconds +/- 0 minutes 49 seconds respectively). In addition, the mean duration of prometaphase and of metaphase are both individually lengthened in the mutant neuroblasts. The mitotic index and metaphase:anaphase ratio are increased in Lis-1G10.14/Lis-1k13209 neuroblasts compared to wild type.

Tension between sister centromeres is reduced in Lis-1G10.14/Lis-1k13209 metaphase neuroblasts compared to wild type.

Homozygous mushroom body neuroblast clones contain only about 50 neurons when examined at the end of larval life or in the adult, a reduction in size compared to control clones. Mutant clones examined at the end of larval life and in the adult are similar in size and clones from 2 week old adults contain a similar number of cells compared to clones from a day old adults. Most neurons in homozygous mushroom body neuroblast clones project their axons only to the medial lobe in adults, indicating that they are γ-type mushroom body neurons. Homozygous mushroom body neuroblast clones induced in newly hatched larvae contain fewer BrdU-positive cells as development progresses, until neuroblast proliferation appears to be arrested at roughly the mid-larval stage, in contrast to wild-type clones, which generate new neurons at all times examined. No obvious defects in nuclear morphology or ploidy are seen at the time of neuroblast-proliferation arrest in mutant clones. Homozygous mushroom body neuroblast clones examined at the end of larval life show a severe reduction in overall dendritic projection compared to wild-type clones. Single cell homozygous clones in the mushroom body examined at the end of larval life show no obvious difference in dendritic complexity compared to wild-type. Single cell homozygous mushroom body clones examined in the adult show a number of dendritic defects; in general the dendrites are shorter than in the wild type and the numbers of primary and higher-order branches and overall branching complexity are reduced. The claw-like structures that are normally present at the end of the terminal branches are present, although they are reduced in number compared to wild type. Axon pathfinding and axonal branching appears normal in homozygous mushroom body neuroblast and single cell clones. Axonal swellings are seen, which are distributed along the length of the axons.

Females containing homozygous germ-line clones fail to produce any eggs. No vitellogenic oocytes are seen in the ovaries. The egg chambers often contain fewer than 16 cells and usually lack an oocyte. All the cells in the mutant cysts appear to develop as nurse cells, as indicated by their polyploid nuclei. The synchrony of the germ-line cell divisions is disrupted as the cell numbers in mutant cysts range consecutively from 1 to 16. The number of cells in the cysts depends on the time of induction of the germ-line clones; the earlier the induction, the fewer cells in the mutant cysts. The frequency of oocyte differentiation is similar in early and late induction. Some mutant cystoblasts fail to divide, while their fusomes continue to grow to a larger sphere and their nuclei sometimes become polyploid. Branched fusomes in the mutant cysts are often thinner than normal and fragmented. Some cystocytes appear arrested in cell division and the nuclei become permaturely polyploid. Fusomes in the more posterior regions of the germarium are sometimes absent and in these cysts the nuclei are often polyploid or apoptotic. Ring canals are morphologically normal in mutant cysts. About 5% of mutant cysts are compound egg chambers that contain a wild-type cyst and some mutant cells. These hybrid cysts are almost always found in association with a mutant cyst. There are usually fewer than 16 combined Lis-1G10.14 cells in the two adjacent cysts. Mosaic egg chambers containing wild-type germ-line cells surrounded by homozygous follicle cells produce normal germ-line cysts of 15 nurse cells and one oocyte.

External Data
Interactions
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Phenotypic Class
Phenotype Manifest In
Suppressed by
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NOT Enhancer of
Statement
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Additional Comments
Genetic Interactions
Statement
Reference

Lis-1 Dys double heterozygous flies (Lis-1G10.14/Df(3R)Exel6184) exhibit indirect flight muscle degeneration.

Lis-1G10.14 DgO86 double heterozygous flies do not exhibit indirect flight muscle degeneration.

One copy of Lis-1G10.14 does not enhance the indirect flight muscle degeneration seen when DysdsRNA.NH2.Scer\UAS is expressed under the control of Scer\GAL4Act.PU.

One copy of Lis-1G10.14 does not enhance the indirect flight muscle degeneration seen when DgdsRNA.Scer\UAS is expressed under the control of Scer\GAL4tub.PU.

Lis-1G10.14 heterozygous germaria overexpressing tkvca.Scer\UAS.P\T under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 exhibit significantly fewer cystoblasts than wild-type germaria overexpressing tkvca.Scer\UAS.P\T.

Expression of constitutively active tkvQ199D.Scer\UAS.P\T in Lis-1G10.14 heterozygous germaria under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 slows the loss of two week old Lis-1G10.14 mutant germline stem cells dramatically. This rescue effect becomes less dramatic for 3 week old mutant germline stem cells.

Germline specific expression of shgScer\UAS.P\T.cCa under the control of Scer\GAL4nos.UTR.T:Hsim\VP16 slows the loss of 2 week old Lis-1G10.14 mutant germline stem cells dramatically and the rescue effect is also decreased for the 3 week old mutant germline stem cells.

The dramatically increased length of the prometaphase/metaphase interval and increase in both mitotic index and metaphase:anaphase ration that is seen in Lis-1G10.14/Lis-1k13209 neuroblasts is not seen if they are also homozygous for rodH4.8, although the centrosome and spindle assembly defects still remain.

BicDD stauunspecified/Lis-1G10.14 triple mutants exhibit a 85% hatch-rate, compared to an 8% hatch-rate in BicDD stauunspecified control strains. This indicates suppression of the BicDD stauunspecified phenotype by Lis-1G10.14.

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

The expression of Lis-1Scer\UAS.cLa is able to rescue the Lis-1k11702/Lis-1G10.14 giant fiber anatomical defects (full rescue when driven by either Scer\GAL4shot-OK307 or Scer\GAL4GMR91H05) and electrophysiological defects (full rescue when driven by Scer\GAL4shot-OK307; partial rescue when driven by Scer\GAL4GMR91H05).

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Mutant
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Stocks (1)
Notes on Origin
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External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (5)
References (14)