Impact of <i>Sim1</i> gene dosage on the development of the paraventricular and supraoptic nuclei of the hypothalamus
Bibliographic record
Abstract
The bHLH-PAS transcription SIM1 is required for the development of all neurons of the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Mice with a loss of Sim1 die within a few days of birth, presumably because of the lack of a PVN and SON. In contrast, mice with a decrease of Sim1 survive, are hyperphagic and become obese. The mechanism by which Sim1 controls food intake remains unclear. Here we show that the development of specific PVN and SON cell types is sensitive to Sim1 gene dosage. Sim1 haploinsufficiency reduces the number of vasopressin (AVP)- and oxytocin-producing cells in the PVN by about 50 and 80%, respectively, but does not affect the development of Crh, Trh and Ss neurons. A decrease of AVP-producing cells increases the sensitivity of Sim1 heterozygous mice to chronic dehydration. Moreover, retrograde labelling showed a 70% reduction of PVN neurons projecting to the dorsal vagal complex, raising the possibility that a decrease of these axons contributes to the hyperphagia of Sim1(+/-) mice. Sim1 haploinsufficiency is thus associated with a decrease of several PVN/SON cell types, which has the potential of affecting distinct homeostatic processes.
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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) | 0.000 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".