Dictyostelium Development Project

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.