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General Information
Symbol
Dmel\twi
Species
D. melanogaster
Name
twist
Annotation Symbol
CG2956
Feature Type
FlyBase ID
FBgn0003900
Gene Model Status
Stock Availability
Gene Snapshot
twist (twi) encodes a transcription factor required for mesoderm cell fate. The product of twi is essential for gastrulation, the development of mesodermal derivatives, including somatic and visceral muscle, fat body and maintenance of muscle stem cells. [Date last reviewed: 2019-03-14]
Key Links
Genomic Location
Cytogenetic map
Sequence location
2R:22,985,374..23,048,325 [+]
Recombination map
2-102
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Protein Family (UniProt)
-
Summaries
Gene Group (FlyBase)
BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS -
Basic helix-loop-helix (bHLH) transcription factors are sequence-specific DNA-binding proteins that regulate transcription. They are characterized by a 60 amino acid region comprising a basic DNA binding domain followed by a HLH motif formed from two amphipathic α-helices connected by a loop. bHLH transcription factors form homo- and hetero-dimeric complexes, which bind to a E box consensus sequence. (Adapted from PMID:15186484).
Protein Function (UniProtKB)
Involved in the establishment and dorsoventral patterning of germ layers in the embryo.
(UniProt, P10627)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
twi: twist
The wild-type allele of twi is involved in the establishment of germ layers. Mutants are embryonic lethals (zygotic), partially dorsalized, and without mesodermal differentiation. A normal blastoderm is formed; at gastrulation, no ventral furrow is visible, but the endoderm invaginates, a cephalic furrow is formed, and the germband elongated. The embryo is twisted or coiled in the egg case, often with posterior side up. There are few mesodermally derived internal tissues. Some embryos fail to make a properly differentiated cuticle, although 40-100% make normal ectodermal derivatives (Simpson, 1983). There is no maternal effect in germline chimeras. twi/+ heterozygous embryos have delayed ventral furrow formation. The TSP of the twi gene is around gastrulation (Thisse et al., 1987).
Summary (Interactive Fly)
transcription factor - bHLH - DV pathway - a switch in the development of muscle - High levels required for somatic myogenesis - this blocks formation of other mesodermal derivatives such as visceral mesoderm and heart
Gene Model and Products
Number of Transcripts
3
Number of Unique Polypeptides
1

Please see the GBrowse view of Dmel\twi or the JBrowse view of Dmel\twi for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Comments on Gene Model
Gene model reviewed during 5.52
Shares 5' exon(s) with upstream non-coding gene; shared promoter (one isoform only of this gene).
Gene model reviewed during 5.56
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0071953
2097
490
FBtr0100130
1883
490
FBtr0345653
2368
490
Additional Transcript Data and Comments
Reported size (kB)
1.9 (longest cDNA)
1.8 (northern blot)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0071864
54.4
490
6.59
FBpp0099476
54.4
490
6.59
FBpp0311714
54.4
490
6.59
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

490 aa isoforms: twi-PA, twi-PB, twi-PC
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Subunit Structure (UniProtKB)
Efficient DNA binding requires dimerization with another bHLH protein. Homodimer.
(UniProt, P10627)
Crossreferences
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\twi using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (21 terms)
Molecular Function (4 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
inferred from direct assay
(assigned by UniProt )
inferred from direct assay
inferred from physical interaction with UniProtKB:P11420
(assigned by UniProt )
inferred from physical interaction with UniProtKB:P10627
(assigned by UniProt )
Terms Based on Predictions or Assertions (0 terms)
Biological Process (15 terms)
Terms Based on Experimental Evidence (10 terms)
CV Term
Evidence
References
inferred from mutant phenotype
(assigned by UniProt )
inferred from expression pattern
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
inferred from mutant phenotype
(assigned by UniProt )
inferred from mutant phenotype
inferred from genetic interaction with FLYBASE:sna; FB:FBgn0003448
inferred from mutant phenotype
(assigned by UniProt )
Terms Based on Predictions or Assertions (7 terms)
CV Term
Evidence
References
Cellular Component (2 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (0 terms)
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
anterior endoderm anlage

Comment: anlage in statu nascendi

mesoderm anlage

Comment: anlage in statu nascendi

trunk mesoderm anlage

Comment: anlage in statu nascendi

cardiogenic mesoderm

Comment: complementary pattern to Socs36E

northern blot
Stage
Tissue/Position (including subcellular localization)
Reference

Comment: reference states 2-10 hr AEL

radioisotope in situ
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Socs36E and twi are expressed in a complementary pattern in the dorsal mesoderm in stage 10 embryos.
Both twi and sna transcript are first detectable during nuclear cycle 12 as a diffuse band half the width of the presumptive mesoderm. Although the expression patterns of sna and twi transcript and protein are similar early in embryogenesis, there are some subtle differences. At mid-cellularization, the sna transcript and protein expression boundaries sharply delimit the presumptive mesoderm. At the same time, twi transcript and protein is expressed in a gradient that extends past the sna expression zone into the presumptive ectoderm. The twi transcript and protein expression pattern gets sharper later, during gastrulation. twi protein is expressed in the mesoderm throughout germ band extension, whereas the sna protein product disappears from the mesoderm partway through germ band extension, and appears in neurectodermal cells which might be neuroblasts.
twi expression is detected in a limited number of ventral cells in stage 5 embryos. The ventral furrow forms shortly thereafter, and twi transcript accumulates in the invaginated cells of the ventral furrow (presumptive mesodermal cells). At stage 8, twi is expressed in the mesodermal layer of the germ band.
The 1.8 kb twi transcript is expressed at high levels between 2 to 6 hr after egg laying, with a peak during gastrulation. The levels of twi transcript are low betwen 8 and 10 hr, and undetectable thereafter.
Marker for
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Protein can be detected in myoblasts in the presumptive and larval wing disc.
Both twi and sna transcript are first detectable during nuclear cycle 12 as a diffuse band half the width of the presumptive mesoderm. Although the expression patterns of sna and twi transcript and protein are similar early in embryogenesis, there are some subtle differences. At mid-cellularization, the sna transcript and protein expression boundaries sharply delimit the presumptive mesoderm. At the same time, twi transcript and protein is expressed in a gradient which overlaps and extends past the sna expression zone into the presumptive ectoderm. The twi transcript and protein expression pattern gets sharper later, during gastrulation. twi protein is expressed in the mesoderm throughout germ band extension, whereas the sna protein product disappears from the mesoderm partway through germ band extension, and appears in neurectodermal cells which might be neuroblasts.
During stage 5 of embryogenesis, the twi protein is expressed ventrally, extending past the anterior and posterior poles. During stage 6, twi protein is seen in the presumptive mesodermal cells of the invaginating ventral furrow, in endodermal cells in the anterior and posterior regions of the embryo, and in the ectodermal cells of the anterior midgut primordium. The mesodermal cells forming the ventral furrow, as well as the four adjoining mesectodermal cells express twi protein at stage 7. At stage 7, twi protein is no longer detected in the cells which will form the posterior midgut rudiment, although labeling is still seen in the anterior midgut rudiment. twi protein becomes restricted to the mesoderm starting at stage 9. In stage 11 embryos, only a few mesodermal cells in each segment express twi protein. At stage 12, a subset of the cells of the somatopleura and the splanchnopleura (mesodermally derived cells which will give rise to the somatic and visceral musculature, respectively) are labeled by anti-twi antibody, and by stage 14, only the splanchnopleura labeling is visible.
Marker for
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
Expression Deduced from Reporters
Reporter: P{-648twi/lacZ}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{-920twi/lacZ}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{-1829twi/lacZ}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{-5000twi/lacZ}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{GAL4-twi.2xPE}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{GAL4-twi.B}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{GAL4-twi.G}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{twi-βgal-1.4a}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{twi-βgal-1.4t}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{twi-βgal-3.0a}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{twi-βgal-3.0t}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{twi-βgal-5.0a}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{twi-βgal-5.0t}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{twi-CD2}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{twi-GAL4.Ga}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{twi-GAL4.U}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{twi-lacZ.1.26}
Stage
Tissue/Position (including subcellular localization)
Reference
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\twi in GBrowse 2
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
FlyExpress - Embryonic expression images (BDGP data)
  • Stages(s) 4-6
  • Stages(s) 7-8
  • Stages(s) 9-10
  • Stages(s) 11-12
  • Stages(s) 13-16
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 21 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 23 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of twi
Transgenic constructs containing regulatory region of twi
Deletions and Duplications ( 11 )
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (26)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
9 of 15
Yes
Yes
 
8 of 15
No
Yes
 
2 of 15
No
No
2 of 15
No
No
 
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (24)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
10 of 15
Yes
Yes
7 of 15
Yes
No
2 of 15
No
No
2 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
 
1 of 15
No
No
 
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Rattus norvegicus (Norway rat) (22)
7 of 13
Yes
Yes
6 of 13
No
Yes
2 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Xenopus tropicalis (Western clawed frog) (14)
4 of 12
Yes
Yes
2 of 12
No
No
2 of 12
No
Yes
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
1 of 12
No
No
Danio rerio (Zebrafish) (25)
8 of 15
Yes
Yes
7 of 15
Yes
No
7 of 15
No
Yes
7 of 15
Yes
No
2 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
Yes
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
1 of 15
No
No
Caenorhabditis elegans (Nematode, roundworm) (3)
9 of 15
Yes
Yes
1 of 15
No
No
1 of 15
No
No
Arabidopsis thaliana (thale-cress) (1)
1 of 9
Yes
Yes
Saccharomyces cerevisiae (Brewer's yeast) (0)
No records found.
Schizosaccharomyces pombe (Fission yeast) (0)
No records found.
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG09190BS5 )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila sechellia
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG09150BW2 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
Mayetiola destructor
Hessian fly
Aedes aegypti
Yellow fever mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W054R )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
Apis mellifera
Western honey bee
Bombus impatiens
Common eastern bumble bee
Bombus terrestris
Buff-tailed bumblebee
Linepithema humile
Argentine ant
Megachile rotundata
Alfalfa leafcutting bee
Nasonia vitripennis
Parasitic wasp
Dendroctonus ponderosae
Mountain pine beetle
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X0511 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Ixodes scapularis
Black-legged tick
Stegodyphus mimosarum
African social velvet spider
Tetranychus urticae
Two-spotted spider mite
Daphnia pulex
Water flea
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G07PB )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Ciona intestinalis
Vase tunicate
Ciona intestinalis
Vase tunicate
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (13)
3 of 10
3 of 10
2 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
1 of 10
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Model Summary Ribbon
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 5 )
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
     
    Disease Associations of Human Orthologs (via DIOPT v7.1 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Functional Complementation Data
    Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
    Interactions
    Summary of Physical Interactions
    esyN Network Diagram
    Show neighbor-neighbor interactions:
    Select Layout:
    Legend:
    Protein
    RNA
    Selected Interactor(s)
    Interactions Browser

    Please see the Physical Interaction reports below for full details
    protein-protein
    Physical Interaction
    Assay
    References
    Summary of Genetic Interactions
    esyN Network Diagram
    esyN Network Key:
    Suppression
    Enhancement

    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Subunit Structure (UniProtKB)
    Efficient DNA binding requires dimerization with another bHLH protein. Homodimer.
    (UniProt, P10627 )
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
    MIST (genetic) - An integrated Molecular Interaction Database
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Gene Group - Pathway Membership (FlyBase)
    External Data
    Linkouts
    SignaLink - A signaling pathway resource with multi-layered regulatory networks.
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    2R
    Recombination map
    2-102
    Cytogenetic map
    Sequence location
    2R:22,985,374..23,048,325 [+]
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    59C2-59C2
    Limits computationally determined from genome sequence between P{PZ}Nup21410444 and P{PZ}l(2)0649606496&P{lacW}l(2)k09913k09913
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    59C3-59D2
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (146)
    Genomic Clones (38)
    cDNA Clones (15)
     

    Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequences
    BDGP DGC clones
    Other clones
    Drosophila Genomics Resource Center cDNA clones

    For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

    cDNA Clones, End Sequenced (ESTs)
    BDGP DGC clones
    RNAi and Array Information
    Linkouts
    DRSC - Results frm RNAi screens
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    Antibody Information
    Other Information
    Relationship to Other Genes
    Source for database identify of
    Source for database merge of
    Additional comments
    Other Comments
    DNA-protein interactions: genome-wide binding profile assayed for twi protein in 2-3 hr embryos; see BDTNP1_TFBS_twi collection report.
    The twi product negatively regulates dac expression in the embryonic head.
    twi homodimers specify mesoderm and the subsequent allocation of mesodermal cells to the somatic muscle fate. twi, da heterodimers repress genes required for somatic myogenesis.
    dl can activate transcription from zen and twi promoters, and additional Dsp1 inhibits the zen activation and increases the twi activation.
    An interplay of dl and twi proteins with Taf4 protein is required for the activation of mesoderm-determining gene expression in the embryo.
    twi and N negatively regulate adult muscle differentiation in Drosophila.
    twi function is required during the late larval stage for splitting of the larval oblique muscles that form the templates of the adult dorsal longitudinal indirect flight muscles.
    twi protein directly regulates Mef2 expression in adult somatic muscle precursor cells via a 175bp enhancer located 2245bp upstream of the Mef2 transcriptional start site. Activation of Mef2 transcription via this enhancer by twi protein is essential for normal adult muscle development.
    In a sample of 79 genes with multiple introns, 33 showed significant heterogeneity in G+C content among introns of the same gene and significant positive correspondence between the intron and the third codon position G+C content within genes. These results are consistent with selection adding against preferred codons at the start of genes.
    The normal location of the ventral furrow in embryos with uniformly expressed fog suggests the existence of a fog-independent pathway determining mesoderm-specific cell behaviours and invagination. Epistasis experiments indicate this pathway requires sna but not twi expression.
    nej is necessary for dl-mediated activation of the twi promoter.
    tin is a direct transcriptional target for twi and its own gene product in visceral mesodermal cells, supporting the idea that twi and tin function in the subdivision of the mesoderm during embryogenesis.
    dl and twi proteins synergistically activate transcription in cell culture from a promoter containing binding sites for both factors. A region outside of the conserved bHLH domain of the twi protein is required for the synergy. Protein-protein interaction assays show that dl and twi proteins bind to one another in vitro.
    Expression of esg in the neuroectoderm is studied, the expression pattern prefigures that of the ASC genes. Dorsoventral pattern of esg expression in the blastoderm is determined by three independent repressive cues (dpp, sna and twi).
    High levels of twi product are required for somatic myogenesis and block the formation of other mesodermal derivatives. Ectopic expression of twi can drive ectodermal cells into myogenesis. After an initial role in gastrulation, twi regulates mesodermal differentiation and propels a specific subset of mesodermal cells into somatic myogenesis.
    Analysis of the motorneuron structure in twi mutant embryos demonstrates post-synaptic target muscles are not required for the outgrowth of presynaptic motor axons into the periphery, nor are they required to induce the expression of genes coding for the components of active zones or for the assembly of active zones themselves. Synthesis of the active zone appears to be an independent function of the presynaptic motorneuron, which is integrated into the development of the neuromuscular synapse.
    At stage 10 two different groups of mesodermal cells can be observed by twi protein expression: group A have weak twi expression and give rise to internal mesodermal structures (visceral mesoderm) and group A have strong twi expression and give rise to external mesodermal structures (heart and somatic mesoderm).
    Mef2 is a downstream target of twi.
    The genomic region of tin contains several twi binding sites suggesting that twi is a direct activator of tin.
    sna is sufficient to induce the formation of an attenuated ventral furrow in the absence of twi+ gene activity. Expression of sna in the absence of twi uncouples ventral furrow formation and mesoderm differentiation, invaginating cells fail to express various mesoderm marker genes.
    twi, sna, hkb and tll gene products define the positions of the primordia of the germ layers and thereby the regions in which the blastoderm epithelium will invaginate.
    Lack of Mef2 gene expression in twi mutant embryos suggests that Mef2 lies downstream in the regulatory pathway.
    The coding region and regulatory regions of twi and Dvir\twi are compared. Within the coding region the basic helix-loop-helix DNA binding and dimerisation domain are highly conserved. A high degree of conservation is seen between the more distal of the two ventral activator elements in the 5' regulatory regions of twi and Dvir\twi. The more proximal ventral activator is missing in the equivalent position in Dvir\twi, instead a region in the second intron resembles the proximal element. Transformation experiments reveal the evolved enhancer elements are similar in structure and functional properties.
    Mesodermal fate is determined where sna and twi but not hkb are expressed. Anteriorly, hkb together with sna determines endodermal fate, and hkb together with twi and sna are required for foregut development.
    The prepattern of the adult musculature, revealed in persistent twi-expressing cells in the embryo, is not dependent on the embryonic peripheral motor nerves.
    twist-expressing cells associate with the segmental nerves in the thoracic as well as the abdominal segments of the third larval instar.
    Promoter fusions using elements of the twi, ve, da and sna promoters indicate that low affinity dl-binding sites restrict target gene expression to the presumptive mesoderm, where there are peak levels of dl expression. The twi promoter includes a proximal and a distal element, and the proximal element contains two low affinity dl binding sites. The proximal element alone directs twi expression in the ventralmost 12 to 14 nuclei while the complete promoter with both proximal and distal elements directs twi expression in the ventralmost 18 to 20 cells. Promoters containing the Et (veinlet) or Eds (dl and snail) E boxes display opposite behaviour in da and twi mutants, suggesting they are regulated by different basic helix loop helix proteins.
    The BRE region of Ubx includes binding sites for hb, ftz, tll, en and twi. The binding of their products and the interplay between them is responsible for generating the expression pattern directed by the BRE.
    In mutant embryos lacking the entire mesoderm or failing to differentiate the visceral mesoderm, the anterior and posterior midgut primordia form but do not migrate properly.
    twi mutants fail to differentiate ventrally derived mesoderm.
    Expression of twi assayed in embryos from females expressing wild type dl and dl-lacZ fusion proteins. Reduction in intensity of twi expression at gastrulation correlates well with degree of dorsalization of embryos, suggesting effect of dl mediated through its downstream target genes.
    A twi binding site has been identified in the neural ectoderm expression region (NEE) of ve promoter: twi activates ve expression. The twi gene is a target gene of dl.
    dl binding site domain exchange experiments, using Ecol\lacZ reporter gene constructs, between the zen and twi promoters demonstrate that dl is intrinsically an activator and that repression requires additional factors present in the distal region of the zen promoter, the VR.
    Deletion analysis of the twi promoter using Ecol\lacZ reporter gene constructs demonstrates that the repressor/activator activity of the dl binding sites depends on its context, not an intrinsic property.
    The zygotically acting DV genes repress ac expression within specific DV domains.
    twi expression marks embryonic precursors of the cells that make the adult muscles.
    twi-expressing lineages of cells have been ablated in the larva, and the impact on muscle pattern in the adult studied.
    A combination of promoter fusion-P-element transformation assays (1.2kb twi promoter fragment is sufficient to generate normal twi pattern of Ecol\lacZ expression) and in vitro DNA binding assays coupled with site directed mutagenesis (revealing four dl-binding sites in the twi promoter) have been used to establish a link between the dl-binding sites and twi expression in early embryos. The dorsal ventral limits of twi expression depend on the number and affinity of dl binding sites present in the twi promoter.
    Establishment of the mesoderm neuroectoderm boundary involves the interaction of twi, sna and dl proteins.
    twi is required for the activation of downstream mesoderm genes.
    Deletion analysis of the twi promoter region using Ecol\lacZ reporter gene construct demonstrate that the region extending from -68 to -269 relative to the transcription start site contains an element that is required for ventral activation of twi in the embryo. This element "z" lies between -55 and -205 and it influences overall promoter strength. A second functional element lies between -537 and -269 and constitutes a ventral activator region. In vitro transcription reactions and S1 nuclease analysis demonstrate the presence of z binding sites within 120bp region of twi promoter proximal to the transcription start site.
    Mutations in zygotic dorsal class gene twi interact with RpII140wimp.
    twi mutant embryos have a few extra neuroblasts around the midline.
    Lateralized embryos have twi expression at the poles. Dorsalized embryos show twi expression during late stages of embryogenesis. Polar expression of twi requires genes of the terminal group. twi is a primary patterning gene for dorsal mesoderm as expression is unaffected by mutations in zygotic dorsal-ventral genes.
    Zygotically active locus involved in the terminal developmental program in the embryo.
    Phenotypic rescue and twi-lacZ expression studies demonstrate that 5' sequences -4.0kb up to +6.2kb 3' sequences are required for normal twi expression. Recurrent deletions in the 3kb twi promoter region have found dl responsive elements (DREs). dl acts as a sequence specific trans-activator of the twi promoter. Gel retardation assays have been used to investigate binding of dl protein to synthetic oligonucleotides corresponding to the proximal and distal activator region of the twi promoter.
    twi and sna have been shown to independently control different aspects of ventral cell behaviour during gastrulation.
    Involved in the regulatory hierarchy responsible for the asymmetric distribution and function of zygotic regulatory gene products along the DV axis of early embryos.
    Molecular analysis of the twi gene and its product reveals that it encodes a nuclear protein expressed in the endoderm and mesoderm anlagen and derived tissues.
    In homozygous embryos invagination of the ventral presumptive mesodermal cells fails to occur and the resulting embryos are devoid of internal organs.
    Mutations in dl, pll, ea, or Tl abolish the expression of twi. At least one dose of dl+ in females is necessary for transcription of twi (Thisse, Stoetzel, El Messal and Perrin-Schmitt, 1987). twi shows extensive identity to a pair of myc-related polypeptides whose dimerized products bind to a sequence in the immunoglobulin kappa chain enhancer; the identical regions have the potential to form two amphipathic helices separated by an intervening loop (Murre, McCaw and Baltimore, 1989).
    The wild-type allele of twi is involved in the establishment of germ layers. Mutants are embryonic lethals (zygotic), partially dorsalized and without mesodermal differentiation. A normal blastoderm is formed; at gastrulation, no ventral furrow is visible, but the endoderm invaginates, a cephalic furrow is formed and the germband elongated. The embryo is twisted or coiled in the egg case, often with posterior side up. There are few mesodermally derived internal tissues. Some embryos fail to make a properly differentiated cuticle, although 40-100% make normal ectodermal derivatives (Simpson, 1983). There is no maternal effect in germ-line chimeras. twi/+ heterozygous embryos have delayed ventral furrow formation. The TSP of the twi gene is around gastrulation (Thisse, Stoetzel, El Messal and Perrin-Schmitt, 1987).
    Origin and Etymology
    Discoverer
    Etymology
    Identification
    External Crossreferences and Linkouts ( 50 )
    Sequence Crossreferences
    NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
    GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
    GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
    RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
    UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
    UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
    Other crossreferences
    BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
    Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
    Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
    Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
    Flygut - An atlas of the Drosophila adult midgut
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
    KEGG Genes - Molecular building blocks of life in the genomic space.
    modMine - A data warehouse for the modENCODE project
    SignaLink - A signaling pathway resource with multi-layered regulatory networks.
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DPiM - Drosophila Protein interaction map
    DroID - A comprehensive database of gene and protein interactions.
    DRSC - Results frm RNAi screens
    FLIGHT - Cell culture data for RNAi and other high-throughput technologies
    FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
    FlyMine - An integrated database for Drosophila genomics
    Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
    InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
    MIST (genetic) - An integrated Molecular Interaction Database
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Synonyms and Secondary IDs (11)
    Reported As
    Symbol Synonym
    twi
    (Ditzler et al., 2019, Johnson and Toettcher, 2019, Shokri et al., 2019, Shorr et al., 2019, Atia et al., 2018, Bischof et al., 2018, Khajouei and Sinha, 2018, Streichan et al., 2018, Batut and Gingeras, 2017, Forés et al., 2017, Koenecke et al., 2017, Nie et al., 2017, Moulton and Letsou, 2016, Sandler and Stathopoulos, 2016, Sandler and Stathopoulos, 2016, Urbansky et al., 2016, Dequéant et al., 2015, Doggett et al., 2015, Fiedler et al., 2015, Hernández et al., 2015, Lin et al., 2015, Monfort and Furlong, 2015.1.15, Rauzi et al., 2015, Schertel et al., 2015, Zhao et al., 2015, Fu et al., 2014, Haye et al., 2014, Jiang and Singh, 2014, Mannervik, 2014, Nie et al., 2014, Pézeron et al., 2014, Rembold et al., 2014, Slattery et al., 2014, Spahn et al., 2014, Tevy et al., 2014, Aleksic et al., 2013, Dresch et al., 2013, Hogan et al., 2013, Ibrahim et al., 2013, Li and Gilmour, 2013, Paul et al., 2013, Saunders et al., 2013, Spahn and Reuter, 2013, Vaque et al., 2013, Vaqué et al., 2013, Webber et al., 2013, Xiong and Zhou, 2013, Aswani et al., 2012, Bonn et al., 2012, Haskel-Ittah et al., 2012, Holmqvist et al., 2012, Japanese National Institute of Genetics, 2012.5.21, Konikoff et al., 2012, Kvon et al., 2012, Rushlow and Shvartsman, 2012, Steiner et al., 2012, Turki-Judeh and Courey, 2012, Wilczynski et al., 2012, Cherbas et al., 2011, Chung et al., 2011, Garcia et al., 2011, Johnson et al., 2011, Kuzin et al., 2011, Li et al., 2011, Lynch and Roth, 2011, Mathew et al., 2011, Mrinal et al., 2011, Nègre et al., 2011, Nien et al., 2011, Ozdemir et al., 2011, Park et al., 2011, Tsurumi et al., 2011, Bernard et al., 2010, Bothma et al., 2010, Cunha et al., 2010, Fernandez-Sanchez et al., 2010, Figeac et al., 2010, Frise et al., 2010, Haghayeghi et al., 2010, Ismat et al., 2010, Jia and Huan, 2010, Martin et al., 2010, Salzer et al., 2010, Wilczyński and Furlong, 2010, Bernard et al., 2009, Christensen et al., 2009.2.28, Liberman and Stathopoulos, 2009, Liu et al., 2009, Martin et al., 2009, Pouille et al., 2009, van Impel et al., 2009, Caussinus et al., 2008, Christensen et al., 2008.12.28, Crocker et al., 2008, Li et al., 2008, Thomas and Cripps, 2008, Wong et al., 2008, Zhang et al., 2008, Aerts et al., 2007, Astigarraga et al., 2007, Beckett and Baylies, 2007, Chen et al., 2007, Dietzl et al., 2007, Sandmann et al., 2007, Seher et al., 2007, Wang et al., 2007, Yan and Lin, 2007, Zeitlinger et al., 2007, Akashi et al., 2006, Anderson et al., 2006, Chen et al., 2006, Choksi et al., 2006, Mohit et al., 2006, Prothmann et al., 2006, Ratnaparkhi et al., 2006, Sandmann et al., 2006, Shapiro and Anderson, 2006, Zinzen et al., 2006, Dutta et al., 2005, Lovato et al., 2005, Stathopoulos and Levine, 2005, Nibu et al., 2003, Jia et al., 2002, Chen et al., 2000, Hewitt et al., 1999)
    Name Synonyms
    Twist
    (Atia et al., 2018, Gilmour et al., 2017, Quijano et al., 2016, Urbansky et al., 2016, Clifford and Adami, 2015, Naval-Sánchez et al., 2015, Housden et al., 2014, Li et al., 2014, Spletter and Schnorrer, 2014, Villar et al., 2014, Zhang et al., 2014, Bardet et al., 2013, Gisselbrecht et al., 2013, Muha and Müller, 2013, Aboukhalil and Bulyk, 2012, Busser et al., 2012, Kvon et al., 2012, Lim and Thiery, 2012, Murray et al., 2012, Ni et al., 2012, Nowak et al., 2012, Schaub et al., 2012, Stojnic et al., 2012, Yáñez-Cuna et al., 2012, Nègre et al., 2011, Razzell et al., 2011, Tsurumi et al., 2011, Bernard et al., 2010, Dutta et al., 2010, Fakhouri et al., 2010, Figeac et al., 2010, Haghayeghi et al., 2010, Haruta et al., 2010, Honkela et al., 2010, Guruharsha et al., 2009, Klingseisen et al., 2009, MacArthur et al., 2009, Papatsenko et al., 2009, Soler and Taylor, 2009, van Impel et al., 2009, Zinzen et al., 2009, Atreya and Fernandes, 2008, Caygill and Johnston, 2008, Desprat et al., 2008, Dougherty et al., 2008, Hong et al., 2008, Koelsch and Leptin, 2008, Levine et al., 2008, McMahon et al., 2008, Nowak et al., 2008, Wu and Sato, 2008, Chandraratna et al., 2007, de Navascués and Modolell, 2007, Fox and Peifer, 2007, Kheradpour et al., 2007, Liotta et al., 2007, Murray and Saint, 2007, Nowak et al., 2007, Orgogozo et al., 2007, Potthoff and Olson, 2007, Sandmann et al., 2007, Stark et al., 2007, Toledano-Katchalski et al., 2007, Wong and Baylies, 2007, Yan and Lin, 2007, Zeitlinger et al., 2007, Zhu et al., 2007, Zinzen and Papatsenko, 2007, Zinzen et al., 2007, Beckett and Baylies, 2006, Blanke and Jackle, 2006, Jang et al., 2006, Philippakis et al., 2006, Sandmann et al., 2006, Sanny et al., 2006, Sivatchenko and Letsou, 2006, Zinzen et al., 2006, Cho, 2004, Harris and Peifer, 2004, Mellerick and Liu, 2004, Bhaskar et al., 2002, Jia et al., 2002, DeLotto, 2001)
    twist
    (Camuglia et al., 2018, Mason et al., 2016, Matsuda et al., 2016, Sandler and Stathopoulos, 2016, Wieschaus and Nüsslein-Volhard, 2016, Chang et al., 2015, Hernández et al., 2015, Lin et al., 2015, Monfort and Furlong, 2015.1.15, Rauzi et al., 2015, Rembold et al., 2014, Aleksic et al., 2013, Fontenele et al., 2013, Ibrahim et al., 2013, Manning et al., 2013, Chiu et al., 2012, Haskel-Ittah et al., 2012, Yang et al., 2012, Mathew et al., 2011, Ozdemir et al., 2011, Aerts et al., 2010, Cunha et al., 2010, Frise et al., 2010, Martin et al., 2010, Neely et al., 2010, Salzer et al., 2010, Tipping et al., 2010, Butler et al., 2009, Cande et al., 2009, Fernandez-Gonzalez et al., 2009, Hurlbut et al., 2009, Kadam et al., 2009, Krejcí et al., 2009, Liu et al., 2009, Martin et al., 2009, Pouille et al., 2009, Sellin et al., 2009, Smith et al., 2009, Widmann and Dahmann, 2009, Atreya and Fernandes, 2008, Bousum et al., 2008, Caussinus et al., 2008, Crocker et al., 2008, Ishihara and Shibata, 2008, Li et al., 2008, Ratnaparkhi et al., 2008, Sokol et al., 2008, Thomas and Cripps, 2008, Wong et al., 2008, Astigarraga et al., 2007, Copley et al., 2007, Duan et al., 2007, Kolsch et al., 2007, Mathew et al., 2007, Peng et al., 2007, Sandmann et al., 2007, Seher et al., 2007, Wang et al., 2007, Maqbool et al., 2006, Montell, 2006, Nguyen and Frasch, 2006, Prothmann et al., 2006, Ratnaparkhi et al., 2006, Sandmann et al., 2006, Taylor, 2006, Zimmermann et al., 2006, Kulkarni and Arnosti, 2005, Leptin, 2005, Gurunathan et al., 2004, Meinhardt, 2004, Zhang et al., 2004, Gullaud et al., 2003, Nibu et al., 2003, Castanon et al., 2001, Roth et al., 1989)
    Secondary FlyBase IDs
    • FBtr0071953
    • FBpp0071864
    Datasets (3)
    Study focus (3)
    Experimental Role
    Project
    Project Type
    Title
    • bait_protein
    ChIP-chip identification of binding sites for transcription factors that regulate mesodermal development.
    • bait_protein
    ChIP characterization of transcription factor genome binding, Berkeley Drosophila Transcription Factor Network Project.
    • bait_protein
    Genome-wide localization of transcription factors by ChIP-chip and ChIP-Seq.
    References (883)