Dictyostelium Development Project

Bottom line: starving Dictyostelium discoideum amoebae aggregate by
relayed cAMP signalling and build a fruiting body of stalk and spores, which
makes this organism the standard model for the step from single cells to
multicellular development. We split development into 14 functional modules,
then reviewed 52 genes across all of them (32 priority genes, 8 direct paralogs
and 12 module-gap genes) and authored 8 Dictyostelium ModuleReview documents,
all status DRAFT. We did this to get a curation-grade picture of a whole
developmental program, and to test how IBA and IEA propagation behaves inside
the organism's large paralog families. The 52 reviews cover 1,478 existing
annotations: 797 accepted, 546 kept as non-core, 42 modified, 37 marked
over-annotated, 19 removed and 37 left undecided. The paralog batch showed
propagation inside families: an aggregation-stage adenylyl-cyclase-activator row
was marked over-annotated on the cAR3 receptor (the paralog notes below say
cAR4), a purinergic-receptor IEA was removed from cAR1, cAR2 and cAR3, and
phosphorelay IEAs were removed from the ACR adenylyl cyclase. The page began as
a scoping enumeration; the status section below records how far it has gone.
Still open are per-gene notes, an expert second pass and the deeper paralog
families. A further completed review, rdeA (the DhkA-to-RegA phosphotransfer
protein), is in genes/DICDI/ but is not yet counted here or grounded in the
SDF-2 module. The other three DICDI reviews in the repo are also outside the
52: mlcD (reviewed before this project) and nip7 and tlcd4b (not
development-specific).

Overview

Dictyostelium discoideum is the premier model for the transition from
unicellular to multicellular life. On starvation, ~10⁵ solitary amoebae
aggregate by relayed cAMP chemotaxis into a mound, which builds a tip, elongates
into a migrating slug (pseudoplasmodium), and finally culminates into a fruiting
body (sorocarp) — a cellular stalk holding aloft a mass of dormant spores. The
whole program runs ~24 h and is driven by cell–cell signaling, chemotaxis,
allorecognition, and a binary prestalk/prespore cell-fate decision.

This project scopes the functional modules that a curation-grade model of
Dictyostelium development must cover, and lists candidate genes (dictyBase
symbols) for review in each. It is a scoping enumeration — UniProt accessions
are intentionally omitted here and should be pulled at review time with
just fetch-gene DICDI <gene> rather than guessed.

Model Species

Dictyostelium discoideum
- UniProt species code / genes/ label: DICDI
- NCBI taxon: 44689
- Reference database: dictyBase (http://dictybase.org)
- Haploid genome, tractable genetics (KO, REMI, RNAi), synchronous development

Developmental Stages (context for the modules)

growth → starvation → aggregation (streams) → mound → tipped mound
      → first finger / slug (migration, phototaxis) → Mexican hat
      → culmination → fruiting body (stalk + spore mass)

Functional Modules

1. Starvation sensing & developmental initiation

Detects nutrient depletion and cell density; commits cells to development.
- yakA — DYRK-family kinase, growth→development switch
- pufA — Pumilio translational repressor of pkaC
- cmfA — conditioned medium factor (cell-density sensing)
- crlA — cAMP receptor-like GPCR (early)
- (concepts: PSF prestarvation factor, CMF quorum sensing)

2. cAMP relay & oscillatory signaling

The core oscillator that produces propagating cAMP waves for aggregation.
- acaA — adenylyl cyclase A (aggregation-stage cAMP synthesis)
- acrA / acgA — adenylyl cyclases (later/culmination)
- carA (cAR1), carB/carC/carD — cAMP receptors (serpentine GPCRs)
- gpaB (Gα2), gpbA (Gβ) — heterotrimeric G proteins
- dagA (CRAC) — cytosolic regulator of adenylyl cyclase (PH-domain)
- erkB (ERK2) — MAP kinase in the relay
- pkaC / pkaR — cAMP-dependent protein kinase catalytic/regulatory subunits
- regA — intracellular cAMP phosphodiesterase (response regulator)
- pdsA — extracellular cAMP phosphodiesterase
- pdiA — extracellular PDE inhibitor

3. Chemotaxis & cell motility (actin cytoskeleton)

Directed movement up cAMP gradients; shared machinery reused throughout.
- rasC, rasG — Ras GTPases (leading-edge signaling)
- pikA / pikB (PI3K), pten — PIP3 gradient (front/back polarity)
- piaA (TorC2/Rip3) — TORC2 for adenylyl cyclase activation & chemotaxis
- mhcA — myosin II heavy chain (rear contraction)
- mlcE, mlcR — myosin II essential/regulatory light chains
- mlcD — myosin light chain (existing review in genes/DICDI/mlcD)
- abpC, corA (coronin), scrA (SCAR/WAVE), arp2/3 — actin regulators

4. Cell–cell adhesion & aggregation

Adhesion systems that hold streams and the mound together.
- csaA (csA / gp80) — contact sites A, EDTA-resistant adhesion
- cadA (ddCAD-1 / gp24) — Ca²⁺-dependent adhesion, early
- tgrC1 (= lagC / gp150) — post-aggregation adhesion + allorecognition ligand
- tgrB1 — allorecognition receptor (TgrB1–TgrC1 self-recognition pair)

Note: lagC / gp150 and tgrC1 are the same gene (UniProt P42523,
TGRC1_DICDI; lagC1 was renamed tgrC1). Curate once, under tgrC1.

5. DIF-1 morphogen: polyketide biosynthesis & signaling

Chlorinated hexaphenone that induces prestalk fate.
- stlA, stlB — steely polyketide synthases (DIF precursor)
- dmtA — des-methyl-DIF-1 methyltransferase (final DIF-1 step)
- chlA — chlorination for DIF-1
- dimA, dimB — bZIP transcription factors mediating DIF response

6. Cell-type patterning: prestalk vs prespore decision

The binary fate choice and its positional markers.
- ecmA, ecmB — prestalk extracellular-matrix / stalk markers
- cudA — nuclear factor for prestalk/culmination
- cotB, cotC, pspA — prespore markers
- (concepts: pstA/pstO/pstB zones, prespore zone, tip organizer)

7. Stalk differentiation & developmental cell death

Terminal stalk cell vacuolization and death.
- ecmB, cudA, stkA (STATa)
- tagB, tagC — ABC-transporter/serine-protease genes for stalk/spore
- autophagy genes (see Module 10) required for stalk cell death

8. Spore differentiation, encapsulation & dormancy

Prespore → mature spore; coat assembly; dormancy maintenance.
- cotA, cotB, cotC — spore coat proteins
- spiA — spore differentiation (late)
- pspA — prespore-specific antigen
- acbA → SDF-2 (acyl-CoA-binding protein, spore-encapsulation signal)
- dhkA, regA — two-component relay gating encapsulation timing
- (concepts: discadenine germination inhibitor, autoactivation)

9. Culmination signaling (SDF / GABA / PKA)

Coordinates the final rise and synchronous sporulation.
- acbA / SDF-2, tagC (protease releasing SDF-2)
- grlE — GABA_B-like receptor; GABA/glutamate signaling in culmination
- pkaC activation as master culmination switch
- dhkA, dhkB, dhkC — histidine kinases feeding regA

10. Autophagy (nutrient recycling & stalk death)

Required for multicellular development and terminal differentiation.
- atg1, atg5, atg6 (beclin), atg7, atg8, atg9 — core autophagy machinery

11. Group-size / cell-counting regulation

Sets the number of cells per fruiting body (breaks streams).
- smlA — represses counting factor secretion
- ctnA (countin), cf45-1, cf50 — counting-factor complex

12. Second messengers for motility (cGMP / Ca²⁺ / IP3)

• gcA, sgcA — guanylyl cyclases (cGMP for myosin assembly)
• gbpA–gbpD — cGMP/cAMP-binding phosphodiesterases & effectors
• iplA — IP3 receptor-like channel; Ca²⁺ signaling

13. Transcriptional regulatory network (GRN)

Stage- and cell-type-specific transcription factors.
- gbfA (GBF) — G-box binding factor, post-aggregative gene master switch
- gtaC, gtaG (GATA) — GATA-family regulators
- statA (Dd-STATa), statB, statC — STAT transcription factors
- srfA (SRF) — spore/late development
- mybE, mybC — Myb regulators (aggregation)
- dimB, cudA, comH — cell-type TFs

14. Morphogenesis: slug migration, phototaxis, thermotaxis

Behavior of the multicellular slug and tip organizer.
- tipA — tip formation
- countin/tip organizer interactions; phototaxis/thermotaxis loci
- (many phototaxis genes are still by locus; curate as identified)

Genes for Review (suggested priority order)

Priority 1 — Core cAMP relay & chemotaxis (~10 genes)

Priority 2 — Adhesion, allorecognition & patterning (~8 genes)

Priority 3 — Terminal differentiation & culmination (~8 genes)

Priority 4 — Regulators, counting & autophagy (~7 genes)

Status & Next Steps

• [x] Enumerate developmental modules and candidate genes (this page)
• [x] Resolve dictyBase symbols → UniProt accessions (fetch-gene DICDI <gene>)
• [x] Fetch GOA + UniProt + cached publications for all priority genes
• [x] Review existing GO annotations for all 32 priority genes (P1–P4) —
  every annotation adjudicated (ACCEPT / KEEP_AS_NON_CORE / MODIFY / REMOVE /
  MARK_AS_OVER_ANNOTATED / UNDECIDED), with description, core_functions, and
  verbatim-quoted supported_by evidence; all pass ai-gene-review validate.
• [x] Reviewed all 32 priority genes (P1–P4) — every annotation adjudicated
  (ACCEPT / KEEP_AS_NON_CORE / MODIFY / REMOVE / MARK_AS_OVER_ANNOTATED /
  UNDECIDED), with description, core_functions, and verbatim-quoted
  supported_by; all pass ai-gene-review validate.
• [x] Reviewed the 8 direct functional paralogs (carB/C/D, acgA, acrA, rasG,
  pkaR, statC) — see families table.
• [x] Closed the remaining module gaps (12 genes) — second messengers,
  DIF-1 biosynthesis, starvation, GRN, morphogenesis (see below). All 14
  enumerated modules now have reviewed representatives.
• [ ] Add per-gene GENE-notes.md deep-research journals where missing
• [ ] Expert sign-off / second-pass QA of the reviews
• [ ] Deeper paralog families still open: wider tgr locus, other Ras/Rap,
  dhk/grl family members, ecm/cot paralogs, statB/statD, additional atg genes

Reviewed genes (52, all validated)

(mlcD was already reviewed prior to this project. tgrC1 = lagC/gp150.)

Module coverage (all 14 represented)

Registered ModuleReview documents

Eight of the developmental modules above are now authored as formal
ModuleReview KB documents in modules/ (each validates
-C ModuleReview, grounds its leaves in the completed DICDI reviews via file:
evidence + PANTHER-family selectors with DICDI representatives, and is named to
signal Dictyostelium scope so it does not collide with generic reusable
modules). The QC panel on each rendered module page auto-joins these gene reviews.

Deliberately NOT registered as dd modules (they would collide with generic,
taxonomically-broad reusable modules): autophagy (Module 10 — kept as the atg1
representative), general chemotaxis/actin motility (Module 3), and the general
transcription GRN (Module 13; its dd TFs are grounded inside the patterning,
relay and starvation modules instead). Stalk death (7) and tip morphogenesis (14)
are left unregistered pending more experimental grounding.

Protein families & paralog coverage

Most reviewed genes are single members of larger Dictyostelium paralog
families — the pipeline caches each gene's PANTHER family at fetch time. The
first pass reviewed one representative per developmental module; the sister
paralogs (which typically perform the same molecular job at a different
developmental stage) remain to be curated. These intra-family sisters are
where IBA/IEA propagation within a family most often produces
over-annotation, so they are high-value targets.

gbfA, cotB, and ctnA map to Dictyostelium-specific / novel families with
no paralog set to chase.

Highest-value paralog batch (direct functional sisters) — ✅ REVIEWED:
carB (cAR2), carC (cAR3), carD (cAR4), acgA (ACG), acrA (ACR),
rasG, pkaR, statC — completing the cAMP receptor series (cAR1–4), the
three developmental adenylate cyclases (ACA/ACG/ACR), the two principal
chemotaxis Ras proteins (RasC/RasG), the PKA holoenzyme (C+R), and a second
STAT. All 8 reviewed and validated.

This batch confirmed the predicted intra-family IBA/IEA over-propagation:
the aggregation-stage "adenylate cyclase-activating cAMP receptor" role was
mis-transferred onto the later paralogs cAR4 (MARK_AS_OVER_ANNOTATED) and the
purinergic-receptor IEA was removed from cAR2/cAR3/cAR4; ACR's degenerate
histidine-kinase/receiver domains carried phosphorelay/transferase IEAs refuted
by its functional paper (REMOVE); statC carried metazoan JAK-STAT / defense /
proliferation terms corrected to STAT signaling and removed.

Still open (lower priority): wider tgr allorecognition locus, remaining
Ras/Rap members, dhk/grl family members, ecm/cot paralogs, statB/statD.

Existing DICDI reviews in the repo

• genes/DICDI/mlcD — myosin light chain (Module 3, motility)
• genes/DICDI/nip7 — ribosome biogenesis (not development-specific)
• genes/DICDI/tlcd4b — TLC-domain lipid metabolism (not development-specific)

Key References (to cite during curation)

Seed the literature at review time; canonical entry points include the
Dictyostelium developmental cell-signaling reviews and dictyBase gene pages.
Record provenance per gene as [PMID:xxxx "supporting text"] in the gene notes.

Slides

• Slides (Marp source: DICTYOSTELIUM_DEVELOPMENT-slides.md) — AI generated