MCD New-Approach-Methodology (NAM) paper map

Curator reference for the malformation-of-cortical-development (MCD) curation cluster seeded from:

Romero DM, Bahi-Buisson N, Francis F. Genetics and mechanisms leading to human cortical malformations. Seminars in Cell & Developmental Biology 76:33–75 (2018). DOI: 10.1016/j.semcdb.2017.09.031

Tracks issue #4100 ("capture iPSC/organoid NAM evidence and modeling patterns for cortical malformation curation"), itself part of the cortical-malformation epic #4098.

Purpose

The review's Section 4 treats stem-cell / organoid systems (NAMs) as the primary tools for studying human-specific cortical-development mechanisms that rodent models miss (most notably basal/outer radial glia, bRG/oRG). This file maps the NAM papers behind that section to verified PubMed identifiers, so that every MCD entry and module in the cluster cites the same, identity-checked references with consistent evidence_source handling.

How this map was built (anti-hallucination methodology)

Per the CLAUDE.md deep-research SOP, review-summary reference numbers and recalled PMIDs are treated as leads, not ground truth. Every PMID below was:

fetched with just fetch-reference PMID:<id> (never hand-created), and
confirmed by reading the cached title / journal / year in references_cache/PMID_<id>.md against the paper the review describes.

Where the issue thread named a specific paper for a Romero reference bracket (e.g. [298] = Bershteyn; [299] = Iefremova; [278] = KATNB1), the bracket is reproduced from the issue. For clusters the issue gives only as a range (e.g. ZIKV [294–297, 309–311]), papers are assigned to the cluster, not to a single bracket number, because the Romero reference list was not independently available to pin exact numbers — the paper identity is verified from the cache, the exact bracket index is not. Unverified bracket→PMID guesses are listed under "Not yet mapped" rather than asserted.

Core curation rule (from #4100)

NAM data — patient-derived iPSC, hESC-derived neural rosettes, neurospheres, cerebral/forebrain organoids, organotypic fetal slices, single-cell profiling of organoids — is mechanistic evidence, classified IN_VITRO, not HUMAN_CLINICAL. Always name the model system in the evidence explanation (e.g. "patient-derived iPSC forebrain organoid", "human cerebral organoid single-cell profiling"). Use the HUMAN_MODEL_MISMATCH discussion kind (not a generic KNOWLEDGE_GAP) when the point is that human organoid/fetal data reveal biology absent or weak in rodent models — the canonical example being bRG/oRG findings.

NAM platform / foundational methods (Romero cluster [282–284, 293] and [288–291])

These establish the platforms themselves; cite them when a node's evidence rests on the validity of the model system rather than a disease-specific finding.

PMID	Verified title (from cache)	First author / journal / year	NAM platform	Cited by (MCD cluster)
16904174	Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.	Takahashi K et al., Cell, 2006	iPSC reprogramming (foundational)	foundational platform reference (fetch-reference-verified; not yet cited in the cluster)
18035408	Induction of pluripotent stem cells from adult human fibroblasts by defined factors.	Takahashi K et al., Cell, 2007	human iPSC reprogramming (foundational)	foundational platform reference (fetch-reference-verified; not yet cited in the cluster)
23995685	Cerebral organoids model human brain development and microcephaly.	Lancaster MA et al., Nature, 2013	cerebral organoid corticogenesis	already in repo cache; cited by `microtubule_dependent_neuronal_migration_failure`, `apical_neuroependyma_integrity_failure`, `pial_basement_membrane_radial_glial_endfoot_failure`, `reelin_terminal_translocation_lamination_failure`
26644564	Human cerebral organoids recapitulate gene expression programs of fetal neocortex development.	Camp JG et al., Proc Natl Acad Sci U S A, 2015	cerebral organoid single-cell corticogenesis validation	already in repo cache (`IN_VITRO`); cited by `microtubule_dependent_neuronal_migration_failure`
24277810	Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex.	Kadoshima T et al., Proc Natl Acad Sci U S A, 2013	hESC-derived 3D neocortex: self-organized axial polarity, inside-out layering, species-specific (human) progenitor-zone dynamics	fetch-reference-verified 2026-07-29; not yet cited in the cluster
26005811	Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture.	Paşca AM et al., Nat Methods, 2015	3D cortical spheroid platform yielding functional cortical neurons and astrocytes (glial arm the 2013–2015 organoid protocols under-represent)	fetch-reference-verified 2026-07-29; not yet cited in the cluster

Which platform paper to cite: Lancaster 23995685 and Kadoshima 24277810 are the two independent 3D-corticogenesis platform anchors; Kadoshima is the better citation when the claim is specifically about human-vs-rodent progenitor-zone dynamics (it reports species-specific progenitor behaviour directly), and is therefore the natural platform reference behind a HUMAN_MODEL_MISMATCH discussion. Camp 26644564 anchors molecular fidelity to fetal neocortex; Paşca 26005811 anchors the astrocyte/glial readout.

Neural rosette / neural-precursor models (Romero cluster `[285–287]`)

The review uses these for the claim that neural rosettes recapitulate apical-basal polarity resembling neural-tube organization, and that neurospheres model self-renewal but lack spatial organization. Cite them for 2D / early neural-precursor claims; they are weaker support than organoids for cortical layering or radial-migration mechanisms (see the NAM hierarchy in #4100).

PMID	Verified title (from cache)	First author / journal / year	NAM platform	Cited by (MCD cluster)
11731781	In vitro differentiation of transplantable neural precursors from human embryonic stem cells.	Zhang SC et al., Nat Biotechnol, 2001	foundational hESC → neural-precursor / rosette derivation	fetch-reference-verified 2026-07-29; not yet cited in the cluster
18198334	Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage.	Elkabetz Y et al., Genes Dev, 2008	neural rosettes as a discrete early neural-stem-cell stage (apical-basal polarity)	fetch-reference-verified 2026-07-29; not yet cited in the cluster
19252484	Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling.	Chambers SM et al., Nat Biotechnol, 2009	dual-SMAD-inhibition neural induction — the standard route to rosettes/NPCs used by most downstream MCD NAM studies	fetch-reference-verified 2026-07-29; not yet cited in the cluster

Scope caveat: a rosette or neurosphere result showing altered self-renewal or polarity supports a progenitor-level node only. Do not use it as evidence for a migration-primary or lamination-primary mechanism — that is exactly the progenitor-vs-migration ambiguity #4101 flags as an open knowledge gap.

Lissencephaly / Miller-Dieker (MDS) organoid models (Romero `[298]`, `[299]`)

PMID	Verified title (from cache)	First author / journal / year	NAM finding	Romero ref	Cited by (MCD cluster)
28111201	Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of Outer Radial Glia.	Bershteyn M et al., Cell Stem Cell, 2017	MDS patient iPSC organoids: neuroepithelial apoptosis, reduced size, altered cleavage angle, defective radial migration rescued by chromosome-17 compensation; prolonged oRG mitosis (human-specific, absent in mouse)	`[298]`	`neural_progenitor_centrosome_spindle_dysfunction`, `microtubule_dependent_neuronal_migration_failure`, `apical_neuroependyma_integrity_failure`, `pial_basement_membrane_radial_glial_endfoot_failure`, `reelin_terminal_translocation_lamination_failure`, `interneuron_specification_tangential_migration_failure`, `KATNB1-related_Cortical_Malformation`, `TUBA1A-related_Tubulinopathy`, `TUBB_TUBB5-related_Microcephaly`, `NDE1-related_Microcephaly_Lissencephaly`
28380362	An Organoid-Based Model of Cortical Development Identifies Non-Cell-Autonomous Defects in Wnt Signaling Contributing to Miller-Dieker Syndrome.	Iefremova V et al., Cell Rep, 2017	MDS forebrain organoids: premature neurogenesis, symmetric→asymmetric apical RGC division switch, altered N-cadherin/β-catenin/Wnt; rescue by Wnt activation	`[299]`	`neural_progenitor_centrosome_spindle_dysfunction`

bRG/oRG note: 28111201's prolonged-oRG-mitosis finding is the cluster's clearest case of a NAM result that disambiguates an entry boundary — oRG biology is a LIS1/MDS-specific feature not shared by DCX or most other LIS genes, and is not reproduced in mouse. Model it with a HUMAN_MODEL_MISMATCH discussion where it bears on lump/split decisions.

Centrosome / spindle progenitor models (Romero `[278]`)

PMID	Verified title (from cache)	First author / journal / year	NAM finding	Romero ref	Cited by (MCD cluster)
25521378	Mutations in KATNB1 cause complex cerebral malformations by disrupting asymmetrically dividing neural progenitors.	Mishra-Gorur K et al., Neuron, 2014	KATNB1 patient-derived cells / progenitor models: disrupted asymmetric progenitor division, defective neuronal production and migration	`[278]`	`neural_progenitor_centrosome_spindle_dysfunction`, `KATNB1-related_Cortical_Malformation`, `Autosomal_Recessive_Primary_Microcephaly`

ZIKV neural-progenitor / organoid models (Romero cluster [294–297, 309–311])

These are the primary mechanistic evidence for the viral progenitor-cytopathy pathway (kb/modules/viral_neural_progenitor_cytopathy.yaml, #4079) and the Congenital Zika Syndrome entry (#4088). All are IN_VITRO except where noted.

PMID	Verified title (from cache)	First author / journal / year	NAM finding	Cited by (MCD cluster)
26952870	Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth.	Tang H et al., Cell Stem Cell, 2016	human iPSC-derived NPCs (hNPCs) are direct ZIKV targets; increased cell death, cell-cycle dysregulation, attenuated growth	`viral_neural_progenitor_cytopathy`, `Congenital_Zika_Syndrome`
27064148	Zika virus impairs growth in human neurospheres and brain organoids.	Garcez PP et al., Science, 2016	reduced viability/growth of human neurospheres and brain organoids → abrogated neurogenesis	`viral_neural_progenitor_cytopathy`, `Congenital_Zika_Syndrome`
27038591	Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells.	Nowakowski TJ et al., Cell Stem Cell, 2016	single-cell expression: candidate entry receptor AXL enriched on human radial glia / astrocytes / endothelium / microglia	`viral_neural_progenitor_cytopathy`, `Congenital_Zika_Syndrome`
27162029	Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3.	Dang J et al., Cell Stem Cell, 2016	hESC-derived cerebral organoids: TLR3 upregulation, perturbed cell fate, reduced organoid volume; TLR3 inhibition partially rescues	`viral_neural_progenitor_cytopathy`, `Congenital_Zika_Syndrome`
27568284	Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia.	Onorati M et al., Cell Rep, 2016	human neuroepithelial stem cells / radial glia: pTBK1 mislocalization, disrupted centrosome/mitosis	`neural_progenitor_centrosome_spindle_dysfunction`, `viral_neural_progenitor_cytopathy`, `Congenital_Zika_Syndrome`
28132835	Recent Zika Virus Isolates Induce Premature Differentiation of Neural Progenitors in Human Brain Organoids.	Gabriel E et al., Cell Stem Cell, 2017	human brain organoids: centrosome perturbation, premature progenitor differentiation → progenitor depletion / cortical thinning	`neural_progenitor_centrosome_spindle_dysfunction`, `viral_neural_progenitor_cytopathy`, `Congenital_Zika_Syndrome`
27279226	The Brazilian Zika virus strain causes birth defects in experimental models.	Cugola FR et al., Nature, 2016	mixed-model: human organoids and mouse / non-human-primate models. Split evidence items so the organoid arm is `IN_VITRO` and the in-vivo arm is `MODEL_ORGANISM`.	`viral_neural_progenitor_cytopathy`, `Congenital_Zika_Syndrome`
27118425	Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure.	Qian X et al., Cell, 2016	forebrain-specific organoids in mini-bioreactors: ZIKV preferentially infects NPCs, reduces proliferation, increases death, and thins the neuronal layer	fetch-reference-verified 2026-07-29; not yet cited in the cluster
27911847	Zika virus cell tropism in the developing human brain and inhibition by azithromycin.	Retallack H et al., Proc Natl Acad Sci U S A, 2016	human astrocyte/NPC and organotypic fetal-brain tropism mapping; azithromycin reduces ZIKV proliferation and cytopathic effect	fetch-reference-verified 2026-07-29; not yet cited in the cluster
29020636	Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection.	Watanabe M et al., Cell Rep, 2017	cerebral organoid screen identified duramycin and ivermectin as active hits; azithromycin was ineffective in this platform despite prior protection in cultured glial cells	fetch-reference-verified 2026-07-29; not yet cited in the cluster
28098253	The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication.	Sacramento CQ et al., Sci Rep, 2017	sofosbuvir rescue: inhibits ZIKV replication in hepatoma (Huh-7) cells, neural stem cells, and brain organoids. All-in-vitro (no in-vivo arm) → `IN_VITRO`.	fetch-reference-verified 2026-07-29; not yet cited in the cluster

Drug-rescue caveat (azithromycin, sofosbuvir): these are mechanistic rescue results in NAM systems, not clinical evidence. Per #4100 they belong on the perturbed causal branch as IN_VITRO support, not in a treatments: block, unless separate clinical evidence for congenital Zika syndrome exists. Azithromycin's effect is platform-dependent: pair Retallack's supportive glial-cell result with Watanabe's refuting cerebral-organoid result rather than recording unqualified support.

Adjacent ZIKV references that are not NAMs (boundary check)

These appear in the same ZIKV evidence base but must not be tagged IN_VITRO — they are listed here so curators don't misclassify them when reusing the cluster's citations.

PMID	Verified title (from cache)	First author / journal / year	Correct `evidence_source`	Why
27179424	Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice.	Li C et al., Cell Stem Cell, 2016	`MODEL_ORGANISM`	in vivo mouse model (despite the journal), not a stem-cell/organoid system
26862926	Zika Virus Associated with Microcephaly.	Mlakar J et al., N Engl J Med, 2016	`HUMAN_CLINICAL`	human fetal autopsy case, not an in-vitro model
24388750	Microcephaly-associated protein WDR62 regulates neurogenesis through JNK1 in the developing neocortex.	Xu D et al., Cell Rep, 2014	`MODEL_ORGANISM`	in vivo developing-neocortex study; cited in MCPH/centrosome context but not a NAM

Rescue-branch modeling reminder

Where an organoid experiment reverses a phenotype, model the rescue as mechanistic evidence on the perturbed causal branch, not as a treatment, unless separate clinical evidence exists:

chromosome-17 compensation rescues bRG mitotic delay — Bershteyn 28111201
Wnt activation rescues premature neurogenesis in MDS organoids — Iefremova 28380362
TLR3 inhibition reduces ZIKV-induced organoid volume loss — Dang 27162029
azithromycin reduces ZIKV proliferation/cytopathic effect in glial cell lines and human astrocytes — Retallack 27911847
sofosbuvir inhibits ZIKV replication in neural stem cells and brain organoids — Sacramento 28098253
duramycin and ivermectin reduce ZIKV infection in cerebral organoids, while azithromycin shows little activity — Watanabe 29020636

Not yet mapped (open follow-ups for this issue)

The following Romero clusters from #4100 are not asserted here because no single PMID could be identity-verified against the cache in this pass. Resolve each with just fetch-reference + cached-title confirmation before citing:

~~Neural rosette / neural-precursor model papers [285–287].~~ Resolved (2026-07-29): three cache-verified anchors now recorded in the new "Neural rosette / neural-precursor models" table — Zhang 11731781, Elkabetz 18198334, Chambers 19252484.
~~The remaining individual cerebral-organoid corticogenesis / single-cell validation papers in [288–291] beyond Lancaster 23995685 (e.g. organoid single-cell transcriptomic validation of corticogenesis pathways).~~ Partially resolved (2026-06-30): the canonical single-cell organoid corticogenesis-validation paper — Camp JG et al. 2015 (PMID:26644564, Human cerebral organoids recapitulate gene expression programs of fetal neocortex development) — was already cache-verified and already cited (IN_VITRO) in microtubule_dependent_neuronal_migration_failure; it is now recorded in the platform table above. Extended (2026-07-29): Kadoshima 24277810 (species-specific progenitor dynamics) and Paşca 26005811 (3D cortical neurons + astrocytes) added to the platform table. Any further [288–291] papers remain open.
~~Any additional ZIKV [309–311] papers (e.g. further AXL / Sofosbuvir rescue reports) beyond the seven verified above.~~ Resolved (2026-07-29): four more cache-verified ZIKV NAM papers added — Qian 27118425, Retallack 27911847, Watanabe 29020636, Sacramento 28098253 (the sofosbuvir rescue report the issue asked for). Exact Romero bracket indices are still not pinned (the reference list was not independently available); papers are assigned to the cluster, per the methodology note above.

Still open:

Exact Romero bracket→PMID indices for the ZIKV and [288–291] clusters (paper identity is verified; bracket number is not).
Neurosphere-specific [285–287] primary papers, as distinct from the rosette/NPC-induction anchors recorded above.

When these are verified, append them to the relevant table above with the same columns and the same cached-title-confirmation standard.

Verification log — recalled PMIDs that were wrong

Recorded because it is direct evidence for the CLAUDE.md rule that recalled or review-summary PMIDs are leads, not ground truth. In the 2026-07-29 pass, two confidently-recalled identifiers turned out to cite unrelated papers, and were caught only by reading the cached title after just fetch-reference:

Recalled as	Actual cached title	Correct PMID
`PMID:24145430` — Kadoshima 2013 hESC neocortex self-organization	Plus-end tracking proteins, CLASPs, and a viral Akt mimic regulate herpesvirus-induced stable microtubule formation and virus spread.	24277810
`PMID:28445721` — Watanabe 2017 ZIKV organoid drug screen	NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain.	29020636

Neither wrong PMID was ever written into a table; both were rejected at the cached-title check. Always read the cache before asserting a mapping.