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>.mdagainst 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 |
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_MISMATCHdiscussion 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 |
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
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]. - ~~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) inmicrotubule_dependent_neuronal_migration_failure; it is now recorded in the platform table above. Any further[288–291]organoid validation papers beyond Lancaster 23995685 and Camp 26644564 remain open. - Any additional ZIKV
[309–311]papers (e.g. further AXL / Sofosbuvir rescue reports) beyond the seven verified above.
When these are verified, append them to the relevant table above with the same columns and the same cached-title-confirmation standard.