Wnt-TCF (canonical Wingless) signaling in Drosophila melanogaster

In canonical Wnt signaling, secreted Wnt proteins, chiefly Wingless, bind Frizzled receptors and the LRP5/6 co-receptor Arrow. Wnt secretion requires palmitoleoylation by Porcupine and transport by Wntless. In the absence of ligand, a destruction complex of Axin, Adenomatous polyposis coli (Apc or Apc2), Casein kinase I alpha and Shaggy (GSK3) phosphorylates Armadillo (beta-catenin) and targets it for degradation. Ligand engagement recruits Dishevelled and Axin to the receptor, inhibiting the destruction complex, so that Armadillo accumulates, enters the nucleus and joins Pangolin (TCF), Legless (BCL9), Pygopus, Chip and Ssdp in a Wnt enhanceosome that activates Wingless target genes. The pathway patterns the embryonic segments, the wing, and many other tissues.

MODULE:dmel_wnt_tcf_signalingDRAFTCONCRETESignaling Pathwaymodules/dmel_wnt_tcf_signaling.yaml
canonical Wnt signaling pathwayGO:0060070
FB:FBgg0000889
FlyBase gene group WNT-TCF: Wnt-tcf signaling pathway
FlyBase release FB2026_03 groups 104 D. melanogaster genes as wnt-tcf signaling pathway (WNT-TCF); this module models that group.
FB:FBgg0000895
FlyBase gene group WNT-E: Wnt enhanceosome
FlyBase release FB2026_03 groups 6 D. melanogaster genes as wnt enhanceosome (WNT-E); this module models that group.
FB:FBgg0001810
FlyBase gene group DES: Beta catenin destruction complexes
FlyBase release FB2026_03 groups 5 D. melanogaster genes as beta catenin destruction complexes (DES); this module models that group.
GO:0060070
canonical Wnt signaling pathway
GO term grounding the module as canonical Wnt signaling pathway.

Boundary. The module combines the FlyBase Wnt-TCF pathway core, Wnt production, the Wnt enhanceosome and the two destruction complex variants. Armadillo, Pangolin, Legless and Pygopus are FlyBase core components and also enhanceosome members; they are modelled once, in the enhanceosome. Axin, Shaggy and Casein kinase I alpha are shared by both destruction complex variants. The SCF-Slimb ubiquitin ligase that degrades phosphorylated Armadillo, the corepressor Groucho and other modulators are FlyBase regulator sets and not parts. Arrow has no molecular function assigned because the GO term for Wnt coreceptor activity is obsolete. FlyBase groups realized by this module: WNT-TCF (FBgg0000889), WNT-E (FBgg0000895), DES (FBgg0001810). Subgroups folded into it: WNT-TCFC, DES-C, WNT-PRO, DES-C2. FlyBase also curates regulator sets for this pathway, which are context and not modelled as parts: WNT-TCFN (negative regulators of wnt-tcf signaling pathway, 43 genes); WNT-TCFP (positive regulators of wnt-tcf signaling pathway, 52 genes). Participants were generated from the FlyBase gene-group membership and mapped to UniProtKB by projects/FLYBASE_GENE_GROUPS/generate_modules.py from module_specs/dmel_wnt_tcf_signaling.yaml. Member genes with a gene review in this repository: sgg.

9Nodes
6Parts
1Variant Sets
2Variants
13Annotons
5Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:dmel_wnt_tcf_signaling deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

3 gene-function check(s) reflected in core functions · 0 conflict(s) · 10 evidence or coverage gap(s) (13 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
wnt_production_por por
UniProtKB:Q9VWV9
Gene
palmitoleoyltransferase activity
GO:1990698
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
wnt_ligands_wg wg
UniProtKB:P09615
Gene
frizzled binding
GO:0005109
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
wnt_ligands_wnt2 Wnt2
UniProtKB:P28465
Gene
frizzled binding
GO:0005109
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
wnt_ligands_wnt6 Wnt6
UniProtKB:Q9VM26
Gene
frizzled binding
GO:0005109
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
wnt_ligands_wnt10 Wnt10
UniProtKB:Q9VM25
Gene
frizzled binding
GO:0005109
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
wnt_receptors_fz fz
UniProtKB:P18537
Gene
Wnt receptor activity
GO:0042813
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
wnt_receptors_fz2 fz2
UniProtKB:Q9VVX3
Gene
Wnt receptor activity
GO:0042813
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
destruction_complex_apc_complex/ckialpha CkIalpha
UniProtKB:P54367
Complex Unit
protein serine/threonine kinase activity
GO:0004674
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
destruction_complex_apc_complex/sgg sgg
UniProtKB:P18431
Complex Unit
protein serine/threonine kinase activity
GO:0004674
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
destruction_complex_apc2_complex/ckialpha CkIalpha
UniProtKB:P54367
Complex Unit
protein serine/threonine kinase activity
GO:0004674
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
destruction_complex_apc2_complex/sgg sgg
UniProtKB:P18431
Complex Unit
protein serine/threonine kinase activity
GO:0004674
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
wnt_enhanceosome_complex/arm arm
UniProtKB:P18824
Complex Unit
transcription coactivator activity
GO:0003713
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
wnt_enhanceosome_complex/pan pan
UniProtKB:Q8IMA8
Complex Unit
DNA-binding transcription factor activity, RNA polymerase II-specific
GO:0000981
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.

Feedback loops (advisory, prose-driven: a regulator counts as "feedback" when its own description says so)

✓ every negative regulator described as feedback has an upstream edge closing the loop.

  • dishevelled ⊣ destruction_complex [closed]
    dishevelled is regulated by wnt_receptors: feedback loop closed
  • destruction_complex ⊣ wnt_enhanceosome [input]
    destruction_complex is a negative regulator with no upstream edge (not described as feedback)

Gene-review completeness (2/21 grounded genes reviewed)

0 complete review(s) · 2 with deep research · 19 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
arr A1Z9D7 ✗ — —
fz2 Q9VVX3 ✓ 69/71 ✓
wg P09615 ✗ — —
fz P18537 ✗ — —
arm P18824 ✗ — —
Wnt2 P28465 ✗ — —
dsh P51140 ✗ — —
CkIalpha P54367 ✗ — —
Chi Q7KVG9 ✗ — —
pan Q8IMA8 ✗ — —
wls Q95ST2 ✗ — —
lgs Q961D9 ✗ — —
Axn Q9V407 ✗ — —
pygo Q9V9W8 ✗ — —
Apc Q9VAS9 ✗ — —
Ssdp Q9VEB9 ✗ — —
Wnt10 Q9VM25 ✗ — —
Wnt6 Q9VM26 ✗ — —
por Q9VWV9 ✗ — —
Apc2 Q9Y1T2 ✗ — —
sgg P18431 ✓ 129/131 ✓

Details

Context
Drosophila melanogasterNCBITaxon:7227
Wnt-TCF signaling pathwaySignaling Pathwaydmel_wnt_tcf_signaling

Wingless/Wnt binding to Frizzled and Arrow inhibits the Axin-APC destruction complex, stabilizing Armadillo, which activates targets with Pangolin/TCF in the Wnt enhanceosome.

canonical Wnt signaling pathwayGO:0060070
Context
Drosophila melanogasterNCBITaxon:7227

Connections

wnt_production -> wnt_ligands Positively Regulates
Porcupine and Wntless are required for Wnt acylation and secretion.
wnt_ligands -> wnt_receptors Positively Regulates
Wnt binds Frizzled and Arrow.
wnt_receptors -> dishevelled Positively Regulates
The ligand-bound receptor recruits Dishevelled.
dishevelled -> destruction_complex Negatively Regulates
Dishevelled and receptor recruitment of Axin inhibit the destruction complex.
destruction_complex -> wnt_enhanceosome Negatively Regulates
The destruction complex targets Armadillo for degradation, preventing enhanceosome activation.
Part 1: ligand acylation and secretion
Wnt productionSignaling Pathwaywnt_production

Annotons

por Wnt production
wnt_production_por
Participant: Gene Product: por
Gene Product:

Function

palmitoleoyltransferase activityGO:1990698

Processes

Wnt protein secretionGO:0061355
wls Wnt production
wnt_production_wls
Participant: Gene Product: wls
Gene Product:

Processes

Wnt protein secretionGO:0061355
Part 2: ligands
Wnt ligandsSignaling Pathwaywnt_ligands

Annotons

Wnt2 Wnt ligands
wnt_ligands_wnt2
Participant: Gene Product: Wnt2
Gene Product:

Function

frizzled bindingGO:0005109
Wnt6 Wnt ligands
wnt_ligands_wnt6
Participant: Gene Product: Wnt6
Gene Product:

Function

frizzled bindingGO:0005109
Wnt10 Wnt ligands
wnt_ligands_wnt10
Participant: Gene Product: Wnt10
Gene Product:

Function

frizzled bindingGO:0005109
Part 3: receptors
Frizzled receptors and Arrow co-receptorSignaling Pathwaywnt_receptors

Annotons

fz Frizzled receptors and Arrow co-receptor
wnt_receptors_fz
Participant: Gene Product: fz
Gene Product:

Function

Wnt receptor activityGO:0042813
fz2 Frizzled receptors and Arrow co-receptor
wnt_receptors_fz2
Participant: Gene Product: fz2
Gene Product:

Function

Wnt receptor activityGO:0042813
arr Frizzled receptors and Arrow co-receptor
wnt_receptors_arr
Participant: Gene Product: arr
Gene Product:
Part 4: cytoplasmic transducer
DishevelledSignaling Pathwaydishevelled

Annotons

dsh Dishevelled
dishevelled_dsh
Participant: Gene Product: dsh
Gene Product:
Part 5: Armadillo phosphorylation and degradation
Beta-catenin destruction complexSignaling Pathwaydestruction_complex
Variant set: Apc or Apc2 destruction complex (One Or More)
Destruction complex, Apc variantSignaling Pathwaydestruction_complex_apc

Annotons

Destruction complex, Apc variant
destruction_complex_apc_complex
Participant: Protein Complex: Destruction complex, Apc variant
Protein Complex:
Destruction complex, Apc variantGO:0030877
Active units:
Apc
Participant: Gene Product: Apc
Gene Product:
Axn
Participant: Gene Product: Axn
Gene Product:
CkIalpha
Participant: Gene Product: CkIalpha
Gene Product:
Function:
protein serine/threonine kinase activityGO:0004674
sgg
Participant: Gene Product: sgg
Gene Product:
Function:
protein serine/threonine kinase activityGO:0004674
Destruction complex, Apc2 variantSignaling Pathwaydestruction_complex_apc2

Annotons

Destruction complex, Apc2 variant
destruction_complex_apc2_complex
Participant: Protein Complex: Destruction complex, Apc2 variant
Protein Complex:
Destruction complex, Apc2 variantGO:0030877
Active units:
Apc2
Participant: Gene Product: Apc2
Gene Product:
Axn
Participant: Gene Product: Axn
Gene Product:
CkIalpha
Participant: Gene Product: CkIalpha
Gene Product:
Function:
protein serine/threonine kinase activityGO:0004674
sgg
Participant: Gene Product: sgg
Gene Product:
Function:
protein serine/threonine kinase activityGO:0004674
Part 6: nuclear transcriptional output
Wnt enhanceosomeSignaling Pathwaywnt_enhanceosome

Armadillo bound to Pangolin on Wnt response elements, with the adaptor Legless, Pygopus, and the Chip-Ssdp complex.

Annotons

Wnt enhanceosome
wnt_enhanceosome_complex
Participant: Protein Complex: Wnt enhanceosome
Protein Complex:
Wnt enhanceosome
Active units:
Chi
Participant: Gene Product: Chi
Gene Product:
Ssdp
Participant: Gene Product: Ssdp
Gene Product:
arm
Participant: Gene Product: arm
Gene Product:
Function:
transcription coactivator activityGO:0003713
lgs
Participant: Gene Product: lgs
Gene Product:
pan
Participant: Gene Product: pan
Gene Product:
Function:
DNA-binding transcription factor activity, RNA polymerase II-specificGO:0000981
pygo
Participant: Gene Product: pygo
Gene Product: