OR22-01 NF-κB Pathway Is Implicated in Thyroid Embryogenesis
Bibliographic record
Abstract
Abstract BACKGROUND: Congenital hypothyroidism due to thyroid dysgenesis (CHTD) is the most common congenital endocrine disease with a prevalence of 1:4,000 live births. We have suggested a two-hit hypothesis to explain CHTD, combining an inherited or de novo variant with a post-zygotic event. This model could explain the sporadicity of the disease (99%), its ethnic predominance and the high discordance rate between monozygotic twins. Despite years of research, more than 95% of cases of CHTD remain unexplained, especially those with thyroid ectopy. This suggests that research on genes and/or pathways not previously associated with thyroid development need to be pursued. Inactivation of the NF-κB pathway can cause deficient anterior pituitary and variable immunodeficiency, or DAVID syndrome. Whether this pathway is also involved in CHTD remains to be established. Objective: To evaluate the implication of the NF-κB pathway during thyroid migration. Methods: Knock down experiments using morpholinos in a zebrafish model were carried out to investigate the roles of certain genes related to the NF-kB pathway during thyroid development. Rescue experiment was also performed to evaluate the specificity of the morpholino. The first gene to be tested was IKBKE, a member of the inhibitor of κB kinase (IKK) family. Thyroid location was assessed by microscopy of live larvae. Results:ikbke depletion in zebrafish caused defective aortic arch artery formation and abnormal thyroid migration. The thyroid phenotype was partially rescued by injection of human IKBKE RNA in ikbke morphants. Conclusion:IKBKE seems important for normal thyroid migration suggesting that the non-canonical NF-kB pathway might be implicated. Further studies targeting other genes in this pathway are ongoing to extend these results.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".