A switch in numb isoforms is a critical step in cortical development
Bibliographic record
Abstract
Loss of numb function suggests that numb maintains progenitors in an undifferentiated state. Herein, we demonstrate that numb1 and numb3 are expressed in undifferentiated cortical progenitors, whereas numb2 and numb4 become prominent throughout differentiation. To further assess the role of different numb isoforms in cortical neural development, we first created a Numb-null state with antisense morpholino, followed by the re-expression of specific numb isoforms. The re-expression of numb1 or numb3 resulted in a significant reduction of neural differentiation, correlating with an expansion of the cortical progenitor pool. In contrast, the expression of numb2 or numb4 resulted in a reduction of proliferating progenitors and a corresponding increase in mammalian achete-scute homologue (MASH1) expression, concurrent with the appearance of the microtubule[corrected]-associated [corrected] protein-2-positive neurons. Of interest, the effect of numb isoforms on neural differentiation could not be directly related to Notch, because classic canonical Notch signaling assays failed to uncover any differences in the four isoforms to inhibit the Notch downstream events. This finding suggests that numb may have other signaling properties during neuronal differentiation in addition to augmenting notch signal strength.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".