FoxA (Sp-FoxA, Q1PA44) — curation notes

Identity

• UniProt Q1PA44 (unreviewed), 440 aa, "Forkhead transcription factor A", gene name FoxA
  (EMBL ABE68834.1). The RX citation is the sea urchin Forkhead family survey
  PMID:17081512.
  Domains (UniProt DR): Fork_head domain IPR001766 (Pfam PF00250), Forkhead N-terminal
  IPR013638 (PF08430), HNF_C IPR018533 (PF09354) — the FoxA/HNF3-type C-terminal region.
  PANTHER PTHR11829 (FORKHEAD BOX PROTEIN), subfamily SF380. The literature gene is
  Sp-foxa of the Davidson endomesoderm GRN; the same forkhead-A orthologue is the one
  studied by Oliveri et al. 2006 and de-Leon & Davidson 2010. No identity doubt: the
  GRN literature refers to a single foxa gene in S. purpuratus.
• No GO-CAM contains this gene (gocams/index.tsv has no STRPU rows).

Place in the GRN

• Endoderm regulatory gene of the veg2 lineage
  PMID:17038513.
• Timing/space: PMID:20479235; cleared from NSM at 18–20 hpf; later also in the oral ectoderm patch where the
  mouth forms.
• At the endoderm/mesoderm split, the outer veg2 ring keeps foxa and loses gcm
  PMID:21623371. Notch perturbation prevents clearance from the mesoderm domain
  PMID:21623371.

Inputs (cis-regulatory analysis, de-Leon & Davidson 2010)

• Four CRMs (F, I, J, K) PMID:20479235.
• Spatial control is a Tcf toggle switch in module F: PMID:20479235; see also PMID:19895806.
• Activating inputs: Su(H) (early boost, module J), Hox11/13b (module K), Otx (modules K and J),
  Brachyury (module I) PMID:19895806.
• Autorepression through a single FoxA site in module I: PMID:20479235; PMID:20479235. Abstract-level statement in
  PMID:17038513.

Outputs / functions (Oliveri et al. 2006; de-Leon 2011 review)

• Three functions: repression of mesodermal fate in veg2 endomesoderm, gut gene expression after
  gastrulation, stomodaeum formation PMID:17038513. MASO phenotype: PMID:17038513 ... no mouth.
• Direct-ish repressive step on gcm: PMID:17038513 PMID:17038513; summarized as PMID:21130759.
• Other known targets: PMID:21130759.
• Foregut endoderm specification: PMID:20479235.
• Gut morphogenesis: PMID:21130759. Boundary maintenance: PMID:20479235.

Curation decisions

• IBA rows (GO:0000978, GO:0000981, GO:0005634, GO:0006357): ACCEPT — Fox forkhead DNA binding is
  family-wide and the sea urchin gene is a documented sequence-specific regulator (autorepression
  via a FoxA site).
• IBA GO:0030154 cell differentiation -> MODIFY to GO:0001714 endodermal cell fate specification.
• IBA GO:0009653 anatomical structure morphogenesis -> MODIFY to GO:0048546 digestive tract
  morphogenesis (gut/mouth failure on knockdown).
• IEA GO:0003677 -> MODIFY to GO:0000978; IEA GO:0003700 -> MODIFY to GO:0000981; IEA GO:0006355
  -> MODIFY to GO:0000122 (documented direction is repression); IEA GO:0043565 ACCEPT;
  IEA GO:0019904 protein domain specific binding (InterPro Fork-head_N) MARK_AS_OVER_ANNOTATED.
• NEW: GO:0001227 (IDA, site mutagenesis), GO:0000122 (IMP/IDA), GO:0001714 (IMP),
  GO:0042662 negative regulation of mesodermal cell fate specification (IMP).
  Comparator check via QuickGO: GO:0001714 is carried by endoderm-specifying TFs (worm end-1,
  med-1/2, zebrafish foxh1, Eomes); GO:0042662 by TFs such as Mesp1 and klf2a/b — so both are
  conventional for a TF that itself performs the regulatory step.
• Not proposed: activator activity (hh activation is reported only second-hand in a review, and the
  post-gastrular gut-gene requirement is necessity evidence), stomodeum/mouth terms (pleiotropic,
  ectodermal role), Hedgehog signalling terms.