Histone Deacetylase 3 Governs Perinatal Cerebral Development via Neural Stem and Progenitor Cells
Bibliographic record
Abstract
We report that cerebrum-specific inactivation of the histone deacetylase 3 (HDAC3) gene causes striking developmental defects in the neocortex, hippocampus, and corpus callosum; post-weaning lethality; and abnormal behaviors, including hyperactivity and anxiety. The defects are due to rapid loss of embryonic neural stem and progenitor cells (NSPCs). Premature neurogenesis and abnormal neuronal migration in the mutant brain alter NSPC homeostasis. Mutant cerebral cortices also display augmented DNA damage responses, apoptosis, and histone hyperacetylation. Moreover, mutant NSPCs are impaired in forming neurospheres in vitro, and treatment with the HDAC3-specific inhibitor RGFP966 abolishes neurosphere formation. Transcriptomic analyses of neonatal cerebral cortices and cultured neurospheres support that HDAC3 regulates transcriptional programs through interaction with different transcription factors, including NFIB. These findings establish HDAC3 as a major deacetylase critical for perinatal development of the mouse cerebrum and NSPCs, thereby suggesting a direct link of this enzymatic epigenetic regulator to human cerebral and intellectual development.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".