Claudin‐6: A novel tight junction molecule is developmentally regulated in mouse embryonic epithelium
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Bibliographic record
Abstract
Embryonic stem (ES) cells differentiating into embryoid bodies (EBs) have been shown to mimic events of very early development and have become a convenient system in which to identify and study early epithelial specific genes. We describe here the primary structure of a mouse epithelial-specific tight junction gene and its expression patterns in differentiating ES cell-derived EBs in vitro. Sequencing of a clone identified by differential display of 4- vs. 6-day-old EB cells revealed it to overlap exactly with a larger cDNA clone (20M24) that had been isolated, but not characterised, in a screen of an ectodermal library. Complete sequencing and analysis of 20M24 revealed an open reading frame for a 219-amino acid protein with structural features of a transmembrane protein. In cell-free reticulocyte lysates, a 20M24 cDNA corresponding to the open reading frame (660 bp) directed the synthesis of a approximately 23-kDa protein that was localized to cell membranes at cell-cell junctions in transfected HEK-293 cells. Database searches indicated that the cDNA was identical to a recently identified member of the Claudin tight junction family, namely Claudin-6. ES cell cultures were used to further examine the expression pattern of Claudin-6 by whole mount in situ hybridisation during aggregation-induced commitment to epithelial differentiation in vitro. The results indicate that Claudin-6 is one of the earliest molecules to be expressed in ES cells committed to the epithelial fate, and the onset of its expression coincides with the expression of the early epithelial marker, keratin 8 (K8). The initiation of expression of Claudin-6 in vitro is dependent upon plating density as well as serum components. In addition, it was found that Claudin-6 expression is inhibited by Noggin, the Bone Morphogenic Protein (BMP)-signalling pathway inhibitor, suggesting that BMPs may be involved in Claudin-6 expression and epithelialization. These studies establish Claudin-6 as a very early marker of epithelialization and provide evidence that the BMP signalling pathway may be one of the ways that its expression is regulated. These studies also support the power of in vitro ES cell technology to identify and screen novel molecules involved in the early epithelialization of the mouse embryo.
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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 | 0.001 |
| 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 it