MeCP2 loss in human cerebral organoids and telencephalic assembloids causes (1)…

MeCP2 loss in human cerebral organoids and telencephalic assembloids causes (1) delayed maturation of cortical excitatory neurons (with preserved gross architecture) and (2) OVERPRODUCTION of cortical interneurons (cINs) with HYPERMOTILE tangential migration dynamics and persistent hypersynchronous network activity. This establishes MeCP2 as a prenatal regulator of inhibitory IN production and tangential migration in human telencephalon, reframing Rett syndrome as having pre-natal origin and implicating cIN dysregulation.

{
  "n": null,
  "doi": "10.1016/j.celrep.2025.116670",
  "claim": "MeCP2 loss in human cerebral organoids and telencephalic assembloids causes (1) delayed maturation of cortical excitatory neurons (with preserved gross architecture) and (2) OVERPRODUCTION of cortical interneurons (cINs) with HYPERMOTILE tangential migration dynamics and persistent hypersynchronous network activity. This establishes MeCP2 as a prenatal regulator of inhibitory IN production and tangential migration in human telencephalon, reframing Rett syndrome as having pre-natal origin and implicating cIN dysregulation.",
  "title": null,
  "cite_key": "Tenreiro2025",
  "evidence": "Cell Reports 2025. Method: hPSC-derived cerebral organoids + telencephalic assembloids; MeCP2-LOF.",
  "effect_size": null,
  "figure_data": null,
  "text_access": "abstract_only",
  "key_entities": [
    "MeCP2",
    "Rett",
    "autism",
    "organoid",
    "assembloid",
    "tangential migration",
    "cortical interneuron",
    "hypermotile",
    "prenatal",
    "human"
  ],
  "study_system": "human telencephalic organoids/assembloids (MeCP2-LOF)",
  "_source_cluster": "cluster_02_development_lineage",
  "replication_status": "single_study",
  "_source_cluster_index": 157,
  "claim_source_sentence": "Loss of MeCP2 led to widespread dysregulation of transcriptional programs associated with cortical excitatory neuron development, accompanied by delayed morphological and functional maturation... MeCP2 deficiency also led to an overproduction of cortical interneurons (cINs), with these cINs exhibiting hypermotile tangential migration dynamics and contributing to persistent hypersynchronous network activity in assembloids.",
  "replication_evidence_dois": [],
  "effect_size_source_sentence": null
}

[
  "paper:paper-708809fbfd02"
]

Loss of MeCP2 led to widespread dysregulation of transcriptional programs associated with cortical excitatory neuron development, accompanied by delayed morphological and functional maturation... MeCP2 deficiency also led to an overproduction of cortical interneurons (cINs), with these cINs exhibiting hypermotile tangential migration dynamics and contributing to persistent hypersynchronous network activity in assemb...

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