Cell-autonomous deletion of the histone methyltransferase DOT1L from Nkx2.1+ MG…

Cell-autonomous deletion of the histone methyltransferase DOT1L from Nkx2.1+ MGE interneuron precursors reduces overall cortical-interneuron numbers from P0, with a disproportionate decrease in parvalbumin (PV) INs. Mitotic cell counts at E14.5 are reduced, indicating premature cell-cycle exit; postmitotic effects on differentiation/migration also contribute, identifying DOT1L as an MGE-IN epigenetic regulator.

{
  "n": null,
  "doi": "10.1093/cercor/bhad281",
  "claim": "Cell-autonomous deletion of the histone methyltransferase DOT1L from Nkx2.1+ MGE interneuron precursors reduces overall cortical-interneuron numbers from P0, with a disproportionate decrease in parvalbumin (PV) INs. Mitotic cell counts at E14.5 are reduced, indicating premature cell-cycle exit; postmitotic effects on differentiation/migration also contribute, identifying DOT1L as an MGE-IN epigenetic regulator.",
  "title": null,
  "cite_key": "Cheffer2023",
  "evidence": "Cerebral Cortex 2023. Method: Nkx2.1-Cre; Dot1l-flox conditional KO; histology + IHC at E14.5/P0/postnatal stages.",
  "effect_size": null,
  "figure_data": null,
  "text_access": "abstract_only",
  "key_entities": [
    "DOT1L",
    "histone methyltransferase",
    "Nkx2.1",
    "MGE",
    "PV",
    "parvalbumin",
    "cell-cycle exit",
    "E14.5",
    "P0",
    "interneuron",
    "epigenetic"
  ],
  "study_system": "Nkx2.1-Cre conditional Dot1l KO mouse",
  "_source_cluster": "cluster_02_development_lineage",
  "replication_status": "single_study",
  "_source_cluster_index": 141,
  "claim_source_sentence": "Deletion of Dot1l in Nkx2.1-expressing interneuron precursor cells results in an overall reduction and altered distribution of GABAergic interneurons in the CP from postnatal day 0 onwards. We observed an altered proportion of GABAergic interneurons in the cortex, with a significant decrease in parvalbumin-expressing interneurons. Moreover, a decreased number of mitotic cells at the embryonic day E14.5 was observed upon Dot1l deletion.",
  "replication_evidence_dois": [],
  "effect_size_source_sentence": null
}

[
  "paper:paper-616950b87f7f"
]

Deletion of Dot1l in Nkx2.1-expressing interneuron precursor cells results in an overall reduction and altered distribution of GABAergic interneurons in the CP from postnatal day 0 onwards. We observed an altered proportion of GABAergic interneurons in the cortex, with a significant decrease in parvalbumin-expressing interneurons. Moreover, a decreased number of mitotic cells at the embryonic day E14.5 was observed...

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