The Expression of the Transcription Factors SNAI1 and SNAI2 Throughout Pre-Implantation Development.
Bibliographic record
Abstract
Mouse preimplantation development is characterized by two distinct morphological events: Compaction and Blastocyst Formation. Compaction is initiated at the 8-cell stage where the assembly of adherens (AJ) and tight junction proteins at the surface of the outer blastomeres begin the process of polarization of the outer cells and eventually provides a permeability seal in the outer cells of the early embryo. In concert with the formation of this seal, the Na/K ATPase establishes an ionic gradient across the trophectoderm (TE), which promotes the movement of fluid through aquaporins to form the blastocyst cavity. The blastocyst consists of two cell types: the TE, which will form the embryonic portion of the placenta, and the inner cell mass (ICM), which consists of the precursor cells that will become the embryo proper. Although we understand the role of many of the proteins involved in blastocyst formation, we have not elucidated how those proteins are regulated throughout preimplantation development. Of these, CDH1, an AJ associated protein, and the ATP1B1, a Na/K ATPase associated protein, are regulated by the transcription factors SNAI1 and SNAI2 in many cell types. SNAI1 and SNAI2 normally function to initiate epithelial-to-mesenchymal transition throughout mouse development. However, SNAI1 and SNAI2 are also oncogenes and aberrant expression of these proteins will promote cancer metastasis. My hypothesis is that Cdh1 and Atp1b1 are both regulated by SNAI1 and SNAI2 throughout mouse preimplantation development. Real-time RT-PCR was applied to determine the steady state mRNA levels of Snai1 and Snai2 throughout preimplantation development. Snai1 steady state mRNA expression increases at the 2-cell stage and then decreases until the 8-cell stage. The steady state mRNA levels returns to the 1-cell level in the blastocyst. Snai2 steady state mRNA levels decrease at the 2-cell stage during the maternal-to-zygotic transition. Expression begins to increase after the 4-cell stage and reaches its peak at the morula stage. Steady state mRNA then decreases at the blastocyst stage. Immunofluorescence was applied to detect SNAI1 and SNAI2 throughout preimplantation development and revealed that SNAI1 and SNAI2 are asymmetrically localized in each blastomere at the 2-cell and the 4-cell stage. SNAI1 and SNAI2 become exclusively distributed to only the outside cells of the developing embryo from the 8-cell stage onward. In the blastocyst, SNAI1 and SNAI2 are only detectable in the TE. SNAI1 and SNAI2 have a unique localization pattern throughout preimplantation development indicative of a role in lineage specification and TE differentiation. Loss-of-Function and Gain-of-Function studies will be applied to determine whether SNAI1 and SNAI2 play a role in TE differentiation and Cdh1 and Atp1b1 regulation. Together, these results provide further insight into the biochemical pathways that regulate blastocyst formation and provide new insight into the normal function of two oncogenes, SNAI1 and SNAI2 during preimplantation development. Research supported by the Canadian Institutes of Health Research. (poster)
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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 | 0.000 | 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".