Skip to content

Add anterior and posterior neural ectoderm terms - #3777

Open
cmungall wants to merge 1 commit into
masterfrom
claude/brain-origins-stgq80
Open

cmungall wants to merge 1 commit into
masterfrom
claude/brain-origins-stgq80

Conversation

@cmungall

Copy link
Copy Markdown
Member

Motivated by a review of Jokhai, Dundes et al. (2026) "Two parallel neural ectoderm progenitors contribute to the developing brain", Nature Neuroscience, PMID:42760324, doi:10.1038/s41593-026-02433-7.

Why

UBERON represents the neural ectoderm only as a single undivided class, neuroectoderm (UBERON:0002346). The earliest regional subdivisions it carries are all neural plate stage or later:

  • pre-chordal neural plate (UBERON:0003056)
  • chordal neural plate (UBERON:0003057)
  • future forebrain (UBERON:0006240)
  • presumptive midbrain (UBERON:0009616)
  • presumptive hindbrain (UBERON:0007277)

The gastrulation-stage anterior/posterior split of the neural ectoderm — described by classical fate maps of zebrafish, frog, chicken and mouse, and characterised molecularly and by lineage tracing in this paper — had no representation, so data annotated to aNE/pNE had nowhere to land except the undivided parent.

The paper's headline result is that the brain does not derive from one common neural ectoderm progenitor. Two arise simultaneously during gastrulation (~E7.5 in mouse): Sox2+ Otx2+ anterior neural ectoderm (forebrain/midbrain) and Sox2+ Gbx2+ posterior neural ectoderm (hindbrain). Acute Gbx2-CreER labelling confines pNE progeny to the hindbrain through E18.5, and hPSC-derived aNE and pNE each fail to adopt the other's identity when challenged with the opposing region-inducing signals.

What

Two new terms, both part_of neuroectoderm (UBERON:0002346):

  • UBERON:9900001 anterior neural ectoderm (aNE)
    SOX2+ OTX2+ GBX2- rostral neural ectoderm; has_potential_to_develop_into forebrain (UBERON:0001890) and midbrain (UBERON:0001891); anterior_to posterior neural ectoderm

  • UBERON:9900002 posterior neural ectoderm (pNE)
    SOX2+ GBX2+ OTX2-low caudal neural ectoderm; has_potential_to_develop_into hindbrain (UBERON:0002028); posterior_to anterior neural ectoderm

Both classify under embryonic tissue (UBERON:0005291) after reasoning.

Each term also carries a homology_notes recording the paper's report of mutually exclusive Otx+/Gbx+ ectodermal domains in mouse, macaque, chicken and zebrafish gastrulae and in the hemichordate Saccoglossus kowalevskii, and a terminology_notes warning curators off conflating these classes with the neural plate and neural tube stage classes listed above.

Modelling decision worth reviewing

The genus is tissue rather than presumptive structure (UBERON:0006598), deliberately; an editor_note on each term records why.

With the presumptive-structure genus, ELK makes aNE a subclass of both future forebrain and presumptive midbrain, and pNE a subclass of presumptive hindbrain, because those three are defined by equivalence as presumptive structure and has_potential_to_develop_into some <region>. Those classes assert develops_from the anterior or posterior neural tube, so the entailment would place a gastrulation-stage domain downstream of the neural tube — which is wrong, and directly contradicts the paper's explicit framing of aNE/pNE as pre-neural-plate populations that precede Sox1/Pax6 expression.

The fate is instead recorded with plain has_potential_to_develop_into relations, which 64 other UBERON classes already use that way. Happy to revisit if there's a preferred idiom for fate-restricted gastrulation-stage domains.

Validation

  • robot convert round-trips src/ontology/uberon-edit.obo unchanged (normalisation clean)
  • robot reason --reasoner ELK completes with no unsatisfiable classes
  • robot report --profile src/ontology/profile.txt flags nothing on either new term (0 ERRORs overall)

Before merge

IDs are in the temporary UBERON:99xxxxx range per CLAUDE.md and need to be minted properly.

Follow-up, not done here

UBERON has no neural plate border / border ectoderm class either, which the same paper's Fig. 1h uses alongside surface ectoderm. That gap is better filled from the neural crest literature than from this paper, where it is a secondary result.

Signed-off-by: @ai4c-agent

🤖 Generated with Claude Code

https://claude.ai/code/session_013vJpYZvvvEbLNxpf9RrV4D


Generated by Claude Code

Motivated by a review of Jokhai, Dundes et al. (2026) "Two parallel neural
ectoderm progenitors contribute to the developing brain", Nature
Neuroscience, PMID:42760324, doi:10.1038/s41593-026-02433-7.

UBERON represents the neural ectoderm only as a single undivided class,
'neuroectoderm' (UBERON:0002346). The earliest regional subdivisions it
carries are neural plate stage or later ('pre-chordal neural plate'
UBERON:0003056, 'chordal neural plate' UBERON:0003057, 'future forebrain'
UBERON:0006240, 'presumptive midbrain' UBERON:0009616, 'presumptive
hindbrain' UBERON:0007277). The gastrulation-stage anterior/posterior
split of the neural ectoderm, which classical fate maps of zebrafish,
frog, chicken and mouse have described and which this paper characterises
molecularly and by lineage tracing, had no representation, so data
annotated to aNE/pNE had nowhere to land except the undivided parent.

Two new terms, both part_of 'neuroectoderm':

- UBERON:9900001 'anterior neural ectoderm' (aNE)
    SOX2+ OTX2+ GBX2- rostral neural ectoderm; has_potential_to_develop_into
    forebrain and midbrain; anterior_to posterior neural ectoderm

- UBERON:9900002 'posterior neural ectoderm' (pNE)
    SOX2+ GBX2+ OTX2-low caudal neural ectoderm; has_potential_to_develop_into
    hindbrain; posterior_to anterior neural ectoderm

Both classify under 'embryonic tissue' (UBERON:0005291) after reasoning.

The genus is 'tissue' rather than 'presumptive structure' (UBERON:0006598),
and this is deliberate; an editor_note on each term records why. With the
presumptive-structure genus, ELK makes aNE a subclass of both 'future
forebrain' and 'presumptive midbrain', and pNE a subclass of 'presumptive
hindbrain', because those three are defined by equivalence as
'presumptive structure and has_potential_to_develop_into some <region>'.
Those classes assert develops_from the anterior or posterior neural tube,
so the entailment would place a gastrulation-stage domain downstream of
the neural tube. The fate is instead recorded with plain
has_potential_to_develop_into relations, which 64 other UBERON classes
already use that way.

Each term also carries a homology_notes recording the paper's report of
mutually exclusive Otx+/Gbx+ ectodermal domains in mouse, macaque, chicken
and zebrafish gastrulae and in the hemichordate Saccoglossus kowalevskii,
and a terminology_notes warning curators off conflating these classes with
the neural plate and neural tube stage classes listed above.

Verified: robot convert round-trips the edit file unchanged (normalisation
clean), robot reason with ELK completes with no unsatisfiable classes, and
robot report with the repo profile flags nothing on either new term.

IDs are in the temporary UBERON:99xxxxx range per CLAUDE.md and need to be
minted properly before merge.

Not done here, noted as a follow-up: UBERON has no 'neural plate border' /
'border ectoderm' class either, which the same paper's Fig. 1h uses
alongside surface ectoderm. That gap is better filled from the neural
crest literature than from this paper, where it is a secondary result.

Signed-off-by: @ai4c-agent

Co-Authored-By: Claude Opus 5 <noreply@anthropic.com>
Claude-Session: https://claude.ai/code/session_013vJpYZvvvEbLNxpf9RrV4D
@ai4c-reviewer

ai4c-reviewer Bot commented Sep 20, 2026

Copy link
Copy Markdown

Claude finished @cmungall's task in 4m 39s —— View job


Review checklist

  • Hierarchy and parents are consistent
  • Definitions and supporting references look adequate — except PMID could not be independently verified (see below)
  • Obsolete or replacement handling is safe (n/a — no obsoletions in this PR)
  • OBO and ODK conventions appear preserved
  • No obvious CI, auth, or workflow regression

Summary

Two new terms, UBERON:9900001 anterior neural ectoderm and UBERON:9900002 posterior neural ectoderm, both part_of neuroectoderm (UBERON:0002346). I checked this diff against src/ontology/uberon-edit.obo with obo-grep.pl (no separate PMID-checking tool worked in this environment — see 🔴 below).

Hierarchy/logic — verified sound. UBERON:0000479 (tissue) and UBERON:0002346 (neuroectoderm) exist as described. I traced the reasoning claim in the PR body by hand: germ layer (UBERON:0000923) asserts part_of UBERON:0000922 ! embryo; neuroectoderm is_a germ layer; embryonic tissue (UBERON:0005291) is defined as tissue and part_of embryo. Since part_of is transitive and the new terms are is_a tissue + part_of neuroectoderm, they do legitimately entail membership in embryonic tissue — the PR's classification claim checks out.

The editor_note's stated reason for using tissue rather than presumptive structure (UBERON:0006598) as genus also checks out: future forebrain (UBERON:0006240), presumptive midbrain (UBERON:0009616) and presumptive hindbrain (UBERON:0007277) are all defined as presumptive structure and has_potential_to_develop_into some <region>, and the last two additionally assert develops_from the anterior/posterior neural tube (UBERON:0009616, UBERON:0007277 confirmed). Avoiding the presumptive structure genus does prevent the (wrong) entailment that a gastrulation-stage domain develops from the neural tube. This is a reasonable, well-documented modelling call.

The terminology_notes correctly describe pre-chordal neural plate (UBERON:0003056, anterior to mid-hindbrain junction) and chordal neural plate (UBERON:0003057, posterior to it, spanning through where the spinal cord arises) — both match what's actually in the edit file.

Relationship types used (anterior_to, posterior_to, has_potential_to_develop_into, dc-contributor) are all valid existing typedefs, reciprocally consistent between the two new terms, and there's no collision with the temporary UBERON:99xxxxx IDs elsewhere in the file. dc-contributor and dcterms-date metadata are present as required by CLAUDE.md.

🔴 CRITICAL: PMID:42760324 / DOI:10.1038/s41593-026-02433-7 could not be verified

Every substantive claim in both new terms — the definitions, the detailed comments (E7.5 Sox2-CreER Confetti lineage tracing, Gbx2-CreER labelling to E18.5, hPSC identity-challenge experiments), and the homology_notes (mouse/macaque/chicken/zebrafish/Saccoglossus) — rests on this single citation, "Jokhai, Dundes et al. (2026), Nature Neuroscience." In this environment all external lookup tools (Europe PMC MCP tools, WebSearch, WebFetch, and direct curl) required an approval step that never resolved, so I was unable to confirm the PMID, DOI, or author names resolve to a real record.
This is a hard blocker per this repo's own rule: "Never guess PMIDs for references, do a web search if needed." Given how specific and mechanistically convenient the described findings are, and that the paper is dated the current year, please have a human confirm the PMID/DOI resolve on PubMed/Europe PMC/Crossref before merge. If the citation doesn't check out, both terms need to be re-sourced or withdrawn.

🔵 SUGGESTION

  • "aNE"/"pNE" synonyms use RELATED OMO:0003000, whereas other abbreviation synonyms in this file (e.g. "FB" BROAD OMO:0003000 on forebrain, "MB" BROAD OMO:0003000 on midbrain) use BROAD. Consider matching that convention for consistency, though RELATED isn't wrong.
  • Neither stanza has a term_tracker_item — understandable since this wasn't filed as an issue first, but worth adding a link to this PR/issue for future traceability.

Not independently re-run

I don't have robot or a working aurelian CLI in this environment (import error: cannot import name 'OpenAIModel'), so I could not re-run robot convert/reason/report myself — I'm relying on the PR author's reported validation results for those.

Recommendation

Requesting changes, solely to get the citation independently verified — the ontology modelling itself is sound and well-reasoned.

@ai4c-reviewer ai4c-reviewer Bot left a comment

Copy link
Copy Markdown

Choose a reason for hiding this comment

The reason will be displayed to describe this comment to others. Learn more.

The ontology modelling in this PR is sound: I traced the reasoning behind the embryonic tissue classification claim and the tissue-vs-presumptive structure genus choice by hand against the edit file, and both check out. Relationship types, reciprocal anterior_to/posterior_to axioms, and metadata (dc-contributor, dcterms-date) are all correctly formed, and there's no ID collision.

Requesting changes for one reason only: every definition, comment, and homology_notes claim on both new terms rests entirely on PMID:42760324 / DOI:10.1038/s41593-026-02433-7 ("Jokhai, Dundes et al. 2026, Nature Neuroscience"), and I was unable to verify this citation resolves to a real record (all external lookup tools were unavailable in my environment). Per this repo's own guidance to never guess PMIDs, please have this confirmed via PubMed/Europe PMC/Crossref before merge — if it doesn't check out, the terms need to be re-sourced.

Full review: see PR comment.

Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment

Labels

None yet

Projects

None yet

Development

Successfully merging this pull request may close these issues.

2 participants