Hedgehog signaling pathway in Drosophila melanogaster

Hedgehog (Hh) is a secreted morphogen that is autoprocessed and modified with cholesterol and, by the acyltransferase Rasp, with palmitate. The transmembrane protein Dispatched releases lipid-modified Hh from producing cells. In receiving cells Hh binds its receptor Patched together with the co-receptors Ihog and Boi. In the absence of Hh, Patched keeps the seven-pass transmembrane protein Smoothened inactive, and the Hedgehog signaling complex of the kinesin-like protein Costal-2 (Cos), the kinase Fused and the zinc-finger transcription factor Cubitus interruptus (Ci) promotes processing of Ci into a repressor form. Hh binding relieves Patched inhibition, Smoothened accumulates at the plasma membrane and recruits the Cos-Fused complex, Ci processing is blocked and full-length Ci activates Hh target genes. The pathway patterns embryonic segments and the anterior-posterior axis of imaginal discs.

MODULE:dmel_hedgehog_signalingDRAFTCONCRETESignaling Pathwaymodules/dmel_hedgehog_signaling.yaml

smoothened signaling pathwayGO:0007224

FB:FBgg0000978

FlyBase gene group HH-SMO: Hedgehog signaling pathway

FlyBase release FB2026_03 groups 98 D. melanogaster genes as hedgehog signaling pathway (HH-SMO); this module models that group.

FB:FBgg0001342

FlyBase gene group HSC: Hedgehog signaling complex

FlyBase release FB2026_03 groups 3 D. melanogaster genes as hedgehog signaling complex (HSC); this module models that group.

GO:0007224

smoothened signaling pathway

GO term grounding the module as smoothened signaling pathway.

Boundary. Core components (FlyBase HH-SMOC), Hh production (HH-PRO) and the Hedgehog signaling complex (HSC). Patched is listed by FlyBase only as a negative regulator (HH-SMON); it is added here as the Hh receptor because the pathway cannot be decomposed without it. Other regulators (PKA, CK1, Sgg, Su(fu), Slimb, glypicans) are not parts. Costal-2 and Fused are also listed by FlyBase as negative regulators, reflecting their roles in Ci processing. FlyBase groups realized by this module: HH-SMO (FBgg0000978), HSC (FBgg0001342). Subgroups folded into it: HH-SMOC, HH-PRO. FlyBase also curates regulator sets for this pathway, which are context and not modelled as parts: HH-SMON (negative regulators of hedgehog signaling pathway, 58 genes); HH-SMOP (positive regulators of hedgehog signaling pathway, 43 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_hedgehog_signaling.yaml. Member genes with a gene review in this repository: boi, ci, cos, disp, fu, hh, ihog, ptc, rasp, smo.

6Nodes

5Parts

0Variant Sets

0Variants

8Annotons

4Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:dmel_hedgehog_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

4 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (4 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.

Annoton	Participant	Function	Assessment
hh_ligand_hh	hh UniProtKB:Q02936 Gene	receptor ligand activity GO:0048018	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hh_reception_ptc	ptc UniProtKB:P18502 Gene	hedgehog receptor activity GO:0008158	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hedgehog_signaling_complex_complex/ci	ci UniProtKB:P19538 Complex Unit	DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hedgehog_signaling_complex_complex/fu	fu UniProtKB:P23647 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).

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.

hh_reception ⊣ smoothened [closed]
hh_reception is regulated by hh_ligand: feedback loop closed

Gene-review completeness (10/10 grounded genes reviewed)

7 complete review(s) · 10 with deep research · 0 missing review · 0 reviewed but lacking deep research

Gene	Review	Complete	Deep research
boi A8JUV7	✓	✓	✓
ci P19538	✓	✓	✓
cos O16844	✓	105/106	✓
disp Q9VNJ5	✓	✓	✓
fu P23647	✓	✓	✓
hh Q02936	✓	155/157	✓
ihog Q9VM64	✓	✓	✓
ptc P18502	✓	54/55	✓
rasp Q9VZU2	✓	✓	✓
smo P91682	✓	✓	✓

Tree

Hedgehog signalingSignaling Pathwaydmel_hedgehog_signaling

Parts
1. 1. ligand modification and secretion
2. Hedgehog lipid modification and releaseSignaling Pathwayhh_production_and_release
  
  Annotons
  - disp Hedgehog lipid modification and release Gene Product: disp
  - rasp Hedgehog lipid modification and release Gene Product: rasp
3. 2. secreted morphogen
4. HedgehogSignaling Pathwayhh_ligand
  
  Annotons
  - hh Hedgehog Gene Product: hh
5. 3. receptor and co-receptors
6. Hedgehog receptionSignaling Pathwayhh_reception
  
  Annotons
  - ptc Hedgehog reception Gene Product: ptc
  - ihog Hedgehog reception Gene Product: ihog
  - boi Hedgehog reception Gene Product: boi
7. 4. seven-pass transmembrane signal transducer
8. SmoothenedSignaling Pathwaysmoothened
  
  Annotons
  - smo Smoothened Gene Product: smo
9. 5. cytoplasmic transducer complex and transcription factor
10. Hedgehog signaling complexSignaling Pathwayhedgehog_signaling_complex
  
  Annotons
  - Hedgehog signaling complex Protein Complex: Hedgehog signaling complex

Details

Context

Drosophila melanogasterNCBITaxon:7227

Hedgehog signalingSignaling Pathwaydmel_hedgehog_signaling

Lipid-modified Hedgehog released by Dispatched binds Patched and Ihog/Boi, activating Smoothened and the Cos-Fused-Ci complex to switch Ci from repressor to activator.

smoothened signaling pathwayGO:0007224

Context

Drosophila melanogasterNCBITaxon:7227

Connections

hh_production_and_release -> hh_ligand Provides Input For

Palmitoylation by Rasp and release by Dispatched produce active, secreted Hh.

hh_ligand -> hh_reception Positively Regulates

Hh binds Patched with the co-receptors Ihog and Boi.

hh_reception -> smoothened Negatively Regulates

Unliganded Patched inhibits Smoothened; Hh binding relieves this inhibition.

smoothened -> hedgehog_signaling_complex Positively Regulates

Active Smoothened recruits Cos-Fused, blocking Ci processing and activating full-length Ci.

Part 1: ligand modification and secretion

Hedgehog lipid modification and releaseSignaling Pathwayhh_production_and_release

Rasp palmitoylates Hh in the secretory pathway; Dispatched is required for release of lipid-modified Hh from producing cells.

Annotons

disp Hedgehog lipid modification and release

hh_production_and_release_disp

Participant: Gene Product: disp

Gene Product:

dispUniProtKB:Q9VNJ5

rasp Hedgehog lipid modification and release

hh_production_and_release_rasp

Participant: Gene Product: rasp

Gene Product:

raspUniProtKB:Q9VZU2

Part 2: secreted morphogen

HedgehogSignaling Pathwayhh_ligand

Annotons

hh Hedgehog

hh_ligand_hh

Participant: Gene Product: hh

Gene Product:

hhUniProtKB:Q02936

Function

receptor ligand activityGO:0048018

Part 3: receptor and co-receptors

Hedgehog receptionSignaling Pathwayhh_reception

Patched is the Hh receptor; Ihog and Boi are cell-surface co-receptors that bind Hh and Patched.

Annotons

ptc Hedgehog reception

hh_reception_ptc

Participant: Gene Product: ptc

Gene Product:

ptcUniProtKB:P18502

Function

hedgehog receptor activityGO:0008158

ihog Hedgehog reception

hh_reception_ihog

Participant: Gene Product: ihog

Gene Product:

ihogUniProtKB:Q9VM64

boi Hedgehog reception

hh_reception_boi

Participant: Gene Product: boi

Gene Product:

boiUniProtKB:A8JUV7

Part 4: seven-pass transmembrane signal transducer

SmoothenedSignaling Pathwaysmoothened

Annotons

smo Smoothened

smoothened_smo

Participant: Gene Product: smo

Gene Product:

smoUniProtKB:P91682

Part 5: cytoplasmic transducer complex and transcription factor

Hedgehog signaling complexSignaling Pathwayhedgehog_signaling_complex

Costal-2, Fused and Cubitus interruptus form a microtubule-associated complex that controls Ci processing and activity. Ci is the transcriptional effector of the pathway.

Annotons

Hedgehog signaling complex

hedgehog_signaling_complex_complex

Participant: Protein Complex: Hedgehog signaling complex

Protein Complex:

Hedgehog signaling complexGO:0035301

Active units:

Participant: Gene Product: ci

Gene Product:

ciUniProtKB:P19538

Function:

DNA-binding transcription factor activity, RNA polymerase II-specificGO:0000981

cos

Participant: Gene Product: cos

Gene Product:

cosUniProtKB:O16844

Participant: Gene Product: fu

Gene Product:

fuUniProtKB:P23647

Function:

protein serine/threonine kinase activityGO:0004674