Regulation of cortical neuron and astrocyte differentiation by the basic helix loop helix protein Hes6
Bibliographic record
Abstract
During development of the mammalian cerebral cortex, pluripotent neural progenitor cells located in the ventricular zone lining the lateral ventricles give rise to neurons, astrocytes, and oligodendrocytes. Neurogenesis precedes astrocyte differentiation, followed by oligodendrocyte differentiation. The mechanisms regulating the transition of undifferentiated progenitor cells into the differentiated state are regulated in part by basic-helix-loop-helix (bHLH) transcription factors of the Hairy/Enhancer of split (Hes) family. A number of Hes proteins are induced in response to the activation of the Notch signaling pathway. Notch-activated Hes proteins, like Hes1 or Hes5, are transcriptional repressors that inhibit cortical neurogenesis and promote astrocyte differentiation. Another Hes family member, termed Hes6, is not activated in response to Notch signaling and promotes neurogenesis, in contrast to Notch-activated Hes1 and Hes5. The objectives of the present studies were a) to elucidate the molecular mechanisms underlying the pro-neuronal activity of Hes6, and b) to determine whether or not Hes6 is also involved in glial cell differentiation. To pursue these goals, a structure function analysis was performed in which mutated forms of Hes6 were examined for their ability to promote neurogenesis using primary cultures of cortical neural progenitor cells. Moreover, Hes6 and mutated forms thereof were tested to determine whether they would inhibit astrocyte differentiation. It is shown here that Hes6 inhibits astrogenesis in addition to inducing neuronal differentiation. These two activities require separate structural domains, suggesting that that they are mediated by different molecular mechanisms.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".