twist1 (Xenopus laevis, P13903) — review notes

Project: NEURAL_CREST_ORIGINS (Tier 1, neural crest specifier candidate).

Identity

Swiss-Prot TWIST_XENLA, 166 aa, X-twi / Xtwi; bHLH (IPR011598, IPR047093 TWIST1_bHLH); C-terminal WR
domain (Twist box, aa 143-166 per Lander 2013). PANTHER PTHR23349 (bHLH Twist family).
UniProt: "Efficient DNA binding requires dimerization with another bHLH protein. Homodimer." Nucleus.

Cloned as Xtwi; mesoderm (notochord, lateral plate, not myotome) from early gastrula, then neural crest
PMID:2590945 PMID:2590945.
Low maternal/pre-gastrula RNA PMID:9727830; function of
early RNA unknown.
In NC: first detectable at stage 14, later than snai1/2, sox9, foxd3; restricted to cranial crest
(mandibular -> hyoid -> branchial), maintained in migrating and post-migratory arch crest
PMID:23443570
PMID:23443570.

Immediate-early Pax3 target in animal caps (cycloheximide-resistant), Pax3-dependent in vivo; not Zic1
PMID:24360906
PMID:24360906.
Pax3 occupancy of a twist1 enhancer not shown.

bHLH; E-box binding and homo-/heterodimerization with E12/E47 (family-level, cited in Lander intro)
PMID:23443570. No Xenopus-specific
DNA-binding / ChIP data found; no direct targets defined in frog.
WR domain binds Snail1/Snail2 directly and inhibits Snail2 (reduces its chromatin recruitment; blocks
Snail2-induced ectopic NC); regulated by GSK3-beta phosphorylation of S148
PMID:23443570
PMID:23443570
PMID:23443570
PMID:23443570.
-> candidate NEW MF GO:0140416 transcription regulator inhibitor activity (IDA).

NC-targeted MO (one cell, 8-cell stage, avoids mesoderm): reduced snai1/2 (mildly), sox10 (strongly);
zic1 domain expanded (cells stalled in border state); no apoptosis/proliferation change; rescued by
MO-resistant Twist PMID:23443570
PMID:23443570.
Fate diversification: MO -> reduced Sox9 in arches, cartilage defects; increased Foxd3 (cranial glia).
GOF -> opposite (more Sox9, less Foxd3) PMID:23443570.
GOF does NOT generate ectopic NC in frog; both gain and loss disrupt NC (stoichiometry-dependent).

Not a border specifier (downstream of Pax3; its loss expands zic1). Not a pluripotency/competence factor.
A late-onset, cranial-restricted NC specifier whose main distinctive output is ectomesenchymal
(chondrogenic) fate of cranial crest. Its GRN-"specifier" status is Xenopus/anamniote-specific:
PMID:23443570
PMID:23443570.
Mouse null still has cranial NC/branchial arch defects PMID:23443570.
GO: GO:0014029 neural crest formation (definition = formation of border ectoderm region) fits the border
layer better; sibling reviews (XENLA/sox10) moved specifier rows to GO:0014036 neural crest cell fate
specification. Applied the same here for consistency.
Cranial skeleton: GO:0048701 embryonic cranial skeleton morphogenesis (mouse Twist1 carries it) — Twist
acts in cranial crest to bias toward cartilage; proposed as NEW (IMP, PMID:23443570).

Mesodermal expression since 1989 is the "ancestral" Twist role (Drosophila twist mesoderm). No Xenopus
functional data for mesoderm found -> no NEW mesoderm term.

Ciona: Twist (twist-like 2) only in mesoderm-derived mesenchyme; misexpression in a9.49 pigment lineage
makes migrating ectomesenchyme
PMID:23135395
PMID:23135395.
Supports co-option of a mesodermal mesenchyme determinant into the cranial crest as a vertebrate innovation.
Amphioxus: many specifier genes absent from the neural plate border
PMID:18562679.
Tetrapods: only cephalic crest expresses Twist and makes ectomesenchyme
PMID:23135395.

Id2/cardiac NC ablation paper (chick, Xenopus), abstract-only cached; abstract does not mention Twist;
presumably Twist used as NC marker in full text. Weak support but term biologically sound -> MODIFY to the
more precise GO:0014036 (consistent with sox10) rather than remove.