snai1 (Snail1, Xsna; P19382) — Xenopus laevis — review notes
Project: NEURAL_CREST_ORIGINS (Tier 3, blastula programme retained in the crest).
Reviewed 2026-10-07. Read alongside genes/XENLA/snai2/ (paralog; Tier 1).
Identity
- P19382 = snai1.L (Xenbase XB-GENE-17344016, chr 9_10L); 259 aa, N-terminal SNAG repression
motif, five C-terminal C2H2 zinc fingers [file:XENLA/snai1/snai1-uniprot.txt "Belongs to the
snail C2H2-type zinc-finger protein family."]. The S homeolog snai1.S is TrEMBL A0A1L8ELB6 and
carries only ARBA IEAs (QuickGO, 2026-10-07).
- Cloned as the frog homologue of Drosophila snail PMID:2226210.
- UniProt function: "Transcriptional repressor. Acts upstream of snai2/slug, zic5 and other neural
crest markers in the specification of the neural crest and neural crest migration. Involved in
embryonic mesoderm formation." [file:XENLA/snai1/snai1-uniprot.txt]
Expression (where / when)
- Maternal (vegetal) and zygotic from stage 9; induced in caps by mesoderm inducers
PMID:2226210.
- All early mesoderm, then tissue-specific down-regulation PMID:8305705.
- Ectoderm from stage 11, in the arc that defines the border, then prospective crest (deep layer)
and roof plate (superficial) PMID:8305705; persists in migrating crest PMID:8305705.
- Precedes slug in the crest PMID:12490555; PMID:24360906.
- Blastula animal-pole (pluripotent) cells co-express Snail1 with Oct/Sox/Vent factors
PMID:25931449.
Molecular activity
- Repressor: Engrailed-repressor fusion of the zinc fingers mimics Snail, E1A-activator fusion
inhibits (Aybar Fig. 8, via deep research); abstract PMID:12490555.
- Corepressors: Ajuba LIM proteins (Ajuba, LIMD1, WTIP) via SNAG PMID:18331720. These are the GOA IPI partners (Xenopus limd1 Q06BR1; mouse
Wtip Q7TQJ8, Ajuba Q91XC0, Limd1 Q9QXD8; identities checked against UniProt REST 2026-10-07)
-> MODIFY protein binding to GO:0001222 transcription corepressor binding (same term snai2 got).
- Elp3 (Q5HZM6) IPI: Elp3 binds the zinc-finger region and blocks beta-Trcp ubiquitination,
stabilising Snail1 PMID:27189455. Upstream regulation of
Snail1 protein, not a Snail1 activity -> REMOVE generic protein binding (as for snai2).
- No ChIP-level direct target in frog. Responsive genes: Delta1 PMID:14681193,
Bmp4 (deep research). Mammalian SNAI1 represses E-cadherin directly (not re-annotated here).
Gain of function
- Sufficient (inducible GR construct) to induce all crest markers tested in embryos and in naive
caps, without neural-plate or mesoderm markers PMID:12490555; PMID:12490555. Slug cannot do this
PMID:12490555.
-> Snai1 has stronger specifier credentials by gain of function than Snai2.
Loss of function
- Dominant-negative / inducible constructs: required for specification and migration; Slug rescues
dn-Snail, so Snail is upstream of Slug PMID:12490555.
- Blastula: blocking Snail1 in animal cells loses pluripotency factors and competence to form
mesoderm and endoderm PMID:25931449. This is a
competence role, not crest specification.
- Caveat: no clean null (MO/CRISPR) for snai1 in frog; reagents (dn zinc-finger constructs) would
hit both homeologs and probably Snai2 targets.
Layer placement (synthesis)
Snail1 occupies TWO layers, sequentially:
1. Competence factor (blastula): co-expressed with, and required to maintain, the
pluripotency network; shared with the crest (Buitrago-Delgado 2015). Same layer as myc-a / id3-a.
No GO term fits (stem cell population maintenance GO:0019827 raised as a question, as for id3-a).
2. Earliest crest specifier: direct Zic1 target in the first wave (with sox8, myc), upstream of
snai2, foxd3, twist, ets1; sufficient in caps; required for specification. -> GO:0014036.
Not a border specifier: it is downstream of Pax3/Zic1 and its activity induces crest rather
than border identity; its early stage-11 "border" expression (Essex 1993) reflects how early it
is activated, not a border-patterning activity.
3. Later: migration (dn-Snail at stage 16 reduces migration; Elp3-stabilised Snail1 needed for
migration) -> GO:0001755 kept, core-ish (EMT effector face).
Non-core: mesoderm formation / gastrulation (expressed in all early mesoderm; mouse Snai1 carries
GO:0001707 by IMP), not annotated in frog — no snai1-specific frog functional evidence; raised as a
question. EMT generically (GO:0001837) not added; the crest-migration term covers the frog data.
Module: belongs in neural_crest_fate_specification (as a Snail-paralog annoton beside snai2, or a
Snail variant set) AND in progenitor_competence_maintenance (one annoton per role). Edge:
zic1_border -> snai1_spec (direct, EMSA); snai1_spec -> snai2_spec (epistasis).
Comparator checks (QuickGO, 2026-10-07)
Query 1: annotation/downloadSearch?goId=GO:0014029,GO:0001755,GO:0014032,GO:0014033&goUsage=descendants&goUsageRelationships=is_a,part_of
(46,708 rows), grep for Snail-family symbols:
- Experimental NC-branch rows on Snail family exist only for frog snai1 (P19382: GO:0014036 IMP,
GO:0001755 IMP), frog snai2 (Q91924: IMP/IGI/IDA) and human SNAI2 (O43623: GO:0014032 IMP,
PMID:12444107).
- Mouse Snai1 (Q02085), human SNAI1 (O95863), zebrafish snai1a/snai1b: no NC-branch term by any
evidence. All other hits are ARBA (GO_REF:0000117) or Ensembl-Compara (GO_REF:0000107) IEAs.
- So Snai1 crest annotation is frog-only. This is partly a coverage gap and partly biology:
in mouse, Snail rather than Slug is in premigratory crest [PMID:12490555 abstract], yet no mouse
crest annotation exists for Snai1. Not used to justify any NEW term.
Query 2: annotation/downloadSearch?geneProductId=Q02085,O95863:
- Both carry GO:0001227 (IDA, IBA); mouse Snai1 carries GO:0001707 mesoderm formation (IMP) and
GO:0001837 EMT; neither carries GO:0001222. Supports NEW GO:0001227 for frog snai1 (frog evidence:
repressor fusion mimicry).
Evolution / outgroups
- Amphioxus: Snail is the one crest specifier at the border PMID:18562679 -> Snail border expression ancestral to chordates.
- Lamprey: one snail gene PMID:39060477, expressed in animal-pole cells and at the
border/crest PMID:39060477, with flat dynamics
PMID:39060477, whereas
Xenopus snai2 rises monotonically like a definitive crest factor.
- Interpretation (subfunctionalisation): the single cyclostome snail combines blastula + border/crest
expression. After the gnathostome duplication, frog snai1 kept the blastula/competence + earliest
border-crest expression (the lamprey-like pattern), while snai2 took the definitive crest
specifier / EMT dynamics. Mouse shows the reverse paralog usage in premigratory crest (Snail, not
Slug), so which paralog leads in the crest is lineage-specific (as for SoxE).
Decisions summary
- 21 GOA rows: ACCEPT 15, MODIFY 5 (protein binding -> GO:0001222 x4; TAS GO:0014029 ->
GO:0014036), REMOVE 1 (Elp3 protein binding). + NEW GO:0001227 (IDA PMID:12490555).
- PMID:15242799 (Id2 cardiac crest paper) is again the AgBase TAS source; miscited (as for snai2,
twist1).