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General Information
Symbol
Dmel\htlAB42
Species
D. melanogaster
Name
FlyBase ID
FBal0057264
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Key Links
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Nucleotide change:

C18047050T

Reported nucleotide change:

C935T

Amino acid change:

R291term | htl-PA; R291term | htl-PB; R291term | htl-PC

Reported amino acid change:

R276term

Comment:

The annotated and reported mutation locations differ by 15aa due to use of a different initiator methione.

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

Nucleotide substitution: C935T.

The premature stop codon is just amino-terminal to the transmembrane domain.

Amino acid replacement: R276term.

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

axon & mechanosensory neuron & adult head, with Scer\GAL4sca-537.4, htlDN.UAS.cMb

axon & mechanosensory neuron & adult head (with htlYY262), with Scer\GAL4Bx-MS1096, Scer\GAL4Mz1277, Scer\GAL4twi.PB, htlUAS.cMa

axon & ocellus sensory structure, with Scer\GAL4sca-537.4, htlDN.UAS.cMb

Detailed Description
Statement
Reference

The size distribution of regenerated adult wings in htlAB42 heterozygous mutants that were subjected to ablation of imaginal wing disc tissue during the larval stage, is significantly shifted towards bigger wing size compared to similarly treated controls.

Antennal lobe ensheathing glia single-cell MARCM clones mutant for htlAB42 exhibit about a 50% reduction in the volume of glial processes accompanied by a significant decrease in the number of glomerular borders to which each glia extends (as compared to control clones).

Astrocyte specification occurs in mutant embryos, as approximately 6 Gat[+] astrocytes per hemisegment are seen located on the dorsal surface of the neuropil in late mutant embryos. However, in contrast to wild type, there is no migration of an astrocyte per hemisegment to a position ventral to the neuropil. The mutant astrocytes show a severe loss of infiltration of processes into the neuropil compared to wild type.

Processes of single cell homozygous astrocyte clones are largely restricted to the surface of the neuropil and the size of the astrocytic domain is severely reduced compared to controls.

Mutant embryos show defects in early mesodermal cell migration, with the cells failing to reach the future dorsal midline. Late stage embryos have a reduced number of dorsal muscles and unfused myoblasts are present. Cardiac and pericardial cells are missing.

Many of the LVM founder cells present in htlAB42 mutant stage 12 embryos lose contact with the trunk visceral mesoderm (TVM) rather than spreading out across it. By stage 13 a large number of rounded and shrunken cells are seen some distance from the TVM.

Stage 11 and 12 mutant embryos have an abnormally shaped cardiogenic mesoderm.

htlAB42/+ third instar larvae have a similar number of boutons per muscle at the neuromuscular junction, compared to controls.

Homozygous glial cell clones in the eye disc are only slightly smaller than wild-type clones, and the mutant cells migrate normally. The mutant clones comprise all glial cell types. However, the mutant cells do not adopt the typical wrapping phenotype, but instead are thin and spindle-shaped.

Homozygous embryos show defects in mesoderm spreading during stage 8, which results in the mesoderm forming a multilayered structure at stages 9-10 (in contrast to wild-type embryos where the mesoderm forms a single layer of cells at this stage).

Mutant embryos show mesoderm cell defects that affect both collapse of the ventral furrow and spreading in the angular direction during gastrulation. The angular movement of upper furrow cells is strongly affected in the mutants. The last cells to invaginate in the mutant embryos, which make up the lower furrow, behave in a similar manner to wild-type furrow cells.

In htlAB42 embryos, the ventral cord is largely uncondensed compared to wild type. The migration of hemocytes during embryonic development appears normal. This phenotype is fully penetrant.

Late stage mutant embryos show variable defects in the shape and location of the corpus cardiacum, from almost normal to stretched out and shifted posteriorly.

htlAB42 mutants exhibit defects in longitudinal visceral muscles. Morphology appears grossly normal in stage 11 and early stage 12 embryos. Longitudinal visceral muscle fibers are all but absent in stage 13 htlAB42 mutant embryos, although circular fiber precursors are essentially normal. The amount of apoptotic cell death is generally increased in htlAB42 mutants.

In stage-15 htlAB42 mutant embryos, the lymph gland, cardioblasts and pericardial nephrocytes fails to develop from the cardiogenic mesoderm.

Cell shape changes in the migrating mesoderm after invagination fail to occur in htlAB42 homozygous embryos. Initially, the mesodermal epithelial tube extends further into the interior of the embryo when compared with wild type. Then, following mitosis in the invaginated mesoderm, the leading edge cells fail to extend dorsolaterally. Some migration does eventually take place and mesodermal cells do undergo some protrusive activity, but they fail to form a monolayer as in wild-type. As a result of these defects, by stage 10-12 there are no eve positive mesodermal cells in any hemisegment. In htlAB42 homozygous embryo, cells at the base of the mesodermal tube at stage 7 fail to attach to underlying ectodermal cells and fail to align along the ventral midline. As in wild-type mesoderm, adherens junctions are lost from the mesoderm in htlAB42 homozygotes after invagination.

No increase is seen in cardioblast numbers in the developing embryo.

Salivary gland shape and position is abnormal in homozygous and htlAB42/htlEMS2 embryos. The visceral mesoderm is disrupted in mutant embryos, showing gaps of variable width.

Pericardial cells fail to form in mutant embryos, due to defects in mesoderm migration.

Homozygous mutants display a defect in mesodermal cell migration. Embryos display an irregular layer where mesodermal cells remain clustered and fail to undergo their complete dorsal migration.

The abnormal pathfinding behaviour in ocellar pioneer (OP) and bristle mechanosensory axons (BM) seen in individuals expressing htlDN.Scer\UAS.cMb under the control of Scer\GAL4sca-537.4 are enhanced by the addition of htlAB42.

htlYY262/htlAB42 flies rescued to the pupal stage by expression of htlScer\UAS.cMa under the control of three drivers (Scer\GAL4Mz1277, Scer\GAL4Bx-MS1096 and Scer\GAL4twi.PB) gives axon guidance phenotypes in the head.

Ocellar pioneer (OP) axons project into the epidermis, bristle mechanosensory (BM) axons fail to project into the brain, or stall in the epidermis or extend apart of epidermis.

Homozygous clones in the eye are wild-type.

Most of the cardial and dorsal somatic muscle cells fail in their dorsal migrations in htlAB42 embryos.

Migration of the mesoderm fails to occur properly in homozygous embryos.

The majority of muscle precursors fail to form in htlAB42 embryos.

The mesodermal cells fail to undergo their normal dorsolateral migration in homozygous embryos and the cells remain aggregated instead of forming a monolayer. Later stage embryos show almost complete loss of cardial and pericardial cells and a marked reduction in the number of dorsal, lateral and ventral groups of somatic muscles. The failure of mesodermal migration is fully rescued by htlScer\UAS.cMa expressed under the control of Scer\GAL4twi.PG.

Mesoderm cells remain close to the ventral midline rather than migrating towards the dorsal ectoderm in homozygous embryos. All eve-positive mesodermal cells are missing. Most of the dorsal somatic muscles, cardial and pericardial cells fail to form. Large gaps are seen in the visceral mesoderm.

Defect in cardiac development, residual pericardial cells are randomly distributed. Most of the dorsal somatic muscles are entirely missing and gaps are seen in the lateral and ventral muscle groups as well, there is both an increasing severity and variability in muscle loss from ventral to dorsal positions of embryos. Visceral musculature fails to undergo its normal morphogenesis (constrictions are not formed). Embryonic mesoderm appears as a multilayed collection of cells on either side of the extended germ band instead of a monolayer beneath the ectoderm.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
NOT suppressed by
Statement
Reference
Enhancer of
NOT Enhancer of
Statement
Reference
Other
Phenotype Manifest In
Enhanced by
Statement
Reference

htlAB42 has mesoderm phenotype, enhanceable by ush1

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

htlAB42/htl[+] is a non-enhancer of neuroblast | larval stage phenotype of trolp4

htlAB42/htl[+] is a non-enhancer of neuroblast | larval stage phenotype of trol13

Other
Additional Comments
Genetic Interactions
Statement
Reference

htlAB42/+ significantly enhances (further reduces) the decreased number of boutons per muscle seen in the neuromuscular junction of third instar Scer\GAL4how-24B>SmndsRNA.C.Scer\UAS.WIZ larvae.

htlAB42/SmnX7 third instar larvae have a significantly decreased number of boutons per muscle at the neuromuscular junction, compared to htlAB42/+ or SmnX7/+.

Expression of btlScer\UAS.T:λ\cI-DD under the control of Scer\GAL4twi.PG is able to induce bilaterally symmetrical flattening of the mesodermal tube onto the ectoderm in htlAB42 embryos. Expression of either btl::EgfrScer\UAS.T:λ\cI-DD or PvrScer\UAS.T:λ\cI-DD under the control of Scer\GAL4twi.PG is not able to rescue either early contact between the mesoderm and ectoderm or symmetric flattening of the mesodermal tube in the early stages of mesoderm morphogenesis in htlAB42 embryos.

trol13/trol13; htlAB42/+ larvae have normal numbers S phase neuroblast.

Expression of btl::htlHB.Scer\UAS or Egfr::htlScer\UAS.cDa under the control of Scer\GAL4twi.PG in htlAB42 embryos partially rescues pericardial cell development; in most cases only 12 to 18 (instead of 20) pericardial cells are properly determined and they often form small clusters instead of being aligned along the anterior-posterior axis. Expression of htl::torScer\UAS.cDa under the control of Scer\GAL4twi.PG in htlAB42 embryos results in the formation of excess pericardial cells.

Embryos heterozygous for htlAB42 and ush1 show a strong mesodermal migration defect. Also about half show a loss of cells from the dorsal mesoderm.

The failure of mesodermal migration is partially rescued by Ras85DG13Q.Scer\UAS expressed under the control of Scer\GAL4twi.PG.

The lack of eve-positive mesodermal cells seen in htlAB42 embryos is partially rescued by btl::EgfrScer\UAS.T:λ\cI-DD expressed under the control of Scer\GAL4twi.PG.

Xenogenetic Interactions
Statement
Reference

Expression of BacA\p35Scer\UAS.cUa under the control of Scer\GAL4alrm.PD in htlAB42 embryos does not rescue infiltration of astrocyte processes into the neuropil or migration of the ventral-most astrocyte.

Expression of Hvul\kringScer\UAS.T:Hsap\MYC under the control of Scer\GAL4htl.POS substantially restores early mesoderm cell migration in htlAB42 embryos.

Expression of Hvul\kringScer\UAS.T:Hsap\MYC under the control of Scer\GAL4htl.POS fails to rescue the loss of dorsal muscles, cardiac or pericardial cells seen in htlAB42 embryos.

Expression of BacA\p35Scer\UAS.cHa under the control of Scer\GAL4tey-5053A partially suppresses the longitudinal visceral muscle (LVM) founder cell migration and survival defects seen in homozygous htlAB42 stage 12/13 embryos. LVM founder cells regain much of the ability to migrate, however their tracks towards the anterior of the embryo are less efficient than in wild type with cells seen veering off in dorsal and ventral directions.

Complementation and Rescue Data
Comments

Expression of htlScer\UAS.cMa under the control of Scer\GAL4alrm.PD strongly restores infiltration of astrocyte processes into the neuropil in htlAB42 embryos, however, migration of the ventral-most astrocyte is not rescued.

Expression of htlScer\UAS.T:λ\cI-DD under the control of Scer\GAL4alrm.PD partially restores infiltration of astrocyte processes into the neuropil in htlAB42 embryos, however, migration of the ventral-most astrocyte is not rescued.

Expression of htlScer\UAS.cMa under the control of Scer\GAL4htl.POS restores dorsal muscle development in approximately half of htlAB42 embryos. Some of the rescued embryos develop cardiac and pericardial cells.

Expression of htlScer\UAS.cMa under the control of Scer\GAL4tey-5053A rescues the longitudinal visceral muscle (LVM) founder cell death seen in htlAB42 mutant stage 13 embryos. The founder cell migration defects are also partially rescued, however some cells acquire abnormal shapes, adhere to positions more distant from the TVM both dorsally and ventrally, and form clusters, resulting in missing LVM cells in the most anterior trunk segments.

Expression of htlScer\UAS.T:λ\cI-DD under the control of Scer\GAL4tey-5053A rescues the longitudinal visceral muscle (LVM) founder cell death seen in htlAB42 mutant stage 13 embryos. The founder cell migration defects are also partially rescued, however some cells acquire abnormal shapes, adhere to positions more distant from the TVM both dorsally and ventrally, and form clusters, resulting in missing LVM cells in the most anterior trunk segments.

htlScer\UAS.cMa; Scer\GAL4twi.PB rescues the migration of the mesoderm after invagination in htlAB42 embryos. As a result the number of hemisegments with eve expressing mesodermal cells is 22, just as in wild-type. In contrast, htlScer\UAS.T:λ\cI-DD ; Scer\GAL4twi.PB rescues the migration of the mesoderm after invagination in htlAB42 embryos, but only partially rescues differentiation of the mesoderm (an average of 12.2 hemisegments per embryo have eve expressing mesodermal cells.

The addition of htlScer\UAS.cMa driven by Scer\GAL4twi.PB, fails to rescue the lethality seen in htlYY262/htlAB42. However, when htlScer\UAS.cMa is driven by Scer\GAL4Mz1277, Scer\GAL4Bx-MS1096 and Scer\GAL4twi.PB concurrently, some escaper pupae do survive.

htlScer\UAS.T:λ\cI-DD partially rescues the mesodermal phenotype of htlAB42 embryos when expressed under the control of Scer\GAL4twi.PG.

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Mutant
Wild-type
Stocks (1)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (6)
References (42)