Prostaglandin E<sub>2</sub> promotes neural proliferation and differentiation and regulates Wnt target gene expression
Bibliographic record
Abstract
Prostaglandin E2 (PGE2 ) is an endogenous lipid molecule that regulates important physiological functions, including calcium signaling, neuronal plasticity, and immune responses. Exogenous factors such as diet, exposure to immunological agents, toxic chemicals, and drugs can influence PGE2 levels in the developing brain and have been associated with autism disorders. This study seeks to determine whether changes in PGE2 level can alter the behavior of undifferentiated and differentiating neuroectodermal (NE-4C) stem cells and whether PGE2 signaling impinges on the Wnt/β-catenin pathways. We show that PGE2 increases proliferation of undifferentiated NE-4C stem cells. PGE2 also promotes the progression of NE-4C stem cell differentiation into neuronal-lineage cells, which is apparent by accelerated appearance of neuronal clusters (neurospheres) and earlier expression of the neuronal marker microtubule-associated protein tau. Furthermore, PGE2 alters the expression of downstream Wnt-regulated genes previously associated with neurodevelopmental disorders. In undifferentiated stem cells, PGE2 downregulates Ptgs2 expression and upregulates Mmp9 and Ccnd1 expression. In differentiating neuronal cells, PGE2 causes upregulation of Wnt3, Tcf4, and Ccnd1. The convergence of the PGE2 and the Wnt pathways is also apparent through increased expression of active β-catenin, a key signaling component of the Wnt/β-catenin pathways. This study provides novel evidence that PGE2 influences progression of neuronal development and influences Wnt target gene expression. We discuss how these findings could have potential implications for neurodevelopmental disorders such as autism. © 2016 Wiley Periodicals, Inc.
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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 | 0.001 | 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) | 0.000 | 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".