fgf8a notes (DANRE, O57341)

2026-09-28 session log

Deep research FAILED for this gene (Edison: 402 Payment Required; the OpenAI key is invalid).
Not retried, per instructions. The literature research below was done by hand, from the
GOA-cited cached publications plus Europe PMC REST searches
(queries: "fgf8b" AND zebrafish; (fgf8a AND fgf8b) AND (duplicat* OR paralog*);
"fgf17a" AND zebrafish; (fgf8b OR "fgf17a") AND zebrafish AND (morpholino OR mutant OR knockdown OR CRISPR);
fgf8a AND fgf8b AND zebrafish).
Newly cached PMIDs this session: 19562753 (Jovelin 2010, FgfD subfamily evolution, full text),
17387144 (Kikuta 2007, genomic regulatory blocks, full text), 28873404 (FGF and somatic gonad,
full text; TGD statement only), 26525676, 21506104, 34462605, 39055102, 40575596 (checked;
little or nothing on the paralog pair, mostly not used). Caution: "Fgf8a/Fgf8b" in mammalian and
some zebrafish papers (PMID:16961592, PMID:21506104, PMID:40575596) refers to the two SPLICE
ISOFORMS of Fgf8, not to the two TGD paralogs. Do not conflate.
Most GOA-cited papers are abstract-only in the cache. Full text available: PMID:12843251,
15281067, 16754885, 17239227, 17448458, 18639539, 19164561, 19395641, 19823566, 20885782,
23789101, 23946439, 24677486, 25142463, 27060628, 28493069, 32345657.

fgf8a is the "uncontested" zebrafish FGF8 orthologue, the gene mutated in acerebellar (ace)
PMID:9609821.
The paralogue fgf8b was first named fgf17 / fgf17a; it is a TGD co-orthologue of FGF8
PMID:17708537.
Synteny: fgf8a on Dre13, fgf8b on Dre1
PMID:19562753.
TGD origin PMID:28873404.
Protein: 210 aa, signal peptide 1-27 (UniProt O57341); 70.8% identity to fgf8b
(compare_pair.py global alignment).

ace ti282a: splice-site point mutation giving a frameshift and premature stop codon, i.e. a
PTC allele that could trigger NMD and, in principle, transcriptional adaptation
PMID:17448458.
Described as a strong hypomorph PMID:17239227.
fgf8 x15 allele used in PMID:24677486 PMID:24677486.
Many annotations rest on morpholinos (fgf8 MO), often combined with fgf3 MO.
No RNA-less (promoter-deletion) fgf8a allele was found in the literature searched.

MHB organizer: PMID:9609821
Heart: PMID:10603341
Only fgf8a (not fgf8b) is expressed in the zebrafish heart; in stickleback the reverse
PMID:19562753
Gastrula D/V: PMID:15151985.
fgf8b is not expressed during gastrulation (UniProt Q805B2; PMID:11091072), so the gastrula roles
(D/V, mesoderm, endoderm restriction) are fgf8a-only at the expression level.
Otic induction with fgf3: PMID:17522161.
Left-right / Kupffer's vesicle: PMID:15932752
PMID:19164561
Ligand spreading, extracellular, lysosomal clearance: PMID:15498491.
fgf8a-only expression domains at long-pec: telencephalon, olfactory epithelium, pharyngeal arches, fin AER
PMID:19562753.
fgf8a keeps the fbxw4-intronic enhancers; the fgf8b block deleted fbxw4
PMID:19782672
PMID:17387144.
Redundancy test (the only one found): ace;noi double mutants (no fgf8a function, no fgf8b/fgf17
expression) show no enhanced dopaminergic phenotype
PMID:12843251.
fgf8b expression at MHB depends on fgf8a for maintenance
PMID:11091072.

120 GOA rows reviewed. MF (growth factor activity, FGFR1/FGFR2 binding), FGFR signaling and
the extracellular location are accepted; the IBA cytoplasm row is marked over-annotated
(secreted ligand with a signal peptide), matching the human FGF8 review.
Experimental developmental rows are ACCEPTed when they describe the best-established
organizer roles (MHB/cerebellum, heart precursors, otic placode, left-right/Kupffer's vesicle,
gastrula D/V) and otherwise KEEP_AS_NON_CORE; they are consistently acts_upstream_of_or_within
readouts of a signalling ligand.
UNDECIDED where the cached abstract gives no support and the claim is not self-evident:
positive regulation of Wnt signaling (PMID:14757644; the abstract describes Wnt8 acting
upstream of Fgf, the reverse direction), and the Fgf19 paper rows (neuron fate specification,
oligodendrocyte differentiation; PMID:16256099).
MODIFY: endoderm development IDA (PMID:17026981) -> negative regulation of endodermal cell fate
specification (GO:0042664), which is what the paper shows.
MARK_AS_OVER_ANNOTATED: regulation of bone remodeling IEP (expression cannot establish
regulation; the IMP row from the same paper is kept).
No NEW terms.