The role of Lkb1 in preimplantation mouse embryos
Bibliographic record
Abstract
LKB1 is a tumor suppressor gene associated with a rare autosomal dominant disorder known as Peutz-Jeghers Syndrome (PJS) which is characterized by the formation of benign gastrointestinal polyps and an increased risk of development of malignant tumors. It has been shown that Lkb1 is involved in various cellular events such cell cycle regulation, cell polarity formation and epithelial morphogenesis, and energy metabolism. The role of Lkb1 in development was examined in Lkb1 KO mice. Interestingly, the homozygous mutant embryos survive up to around E9.5 and die due to vasuclogenesis defects. Although cell polarity and epithelial morphogenesis play important roles in cell allocation and lineage specification in the preimplantation embryos, no clear defect was observed.We hypothesize that lack of early phenotypes in the Lkb1 mutant embryo is because maternal loaded Lkb1 protein and mRNA are sufficient for the embryo to go through the early stages. To test this, we generated maternal/zygotic null Lkb1 embryos using the oocyte specific Cre line, ZP3-Cre (a recombinase enzyme that is active in the oocytes) with the floxed Lkb1 conditional KO mouse line. Interestingly, both maternal/zygotic-deleted homozygous (MZLkb1-/-) embryos and maternal-deleted heterozygous (MLkb1+/-) embryos established epithelial layers at E3.5 and E4.5 with clear apico-basal polarity. Although the first three cell lineages, trophoectoderm, epiblast and primitive endoderm were formed, we found a bias towards a particular cell fate; the PE lineage, at E3.5 in the both MLkb1+/- and MZLkb1-/- embryos.We also found changes in cell allocation and ICM morphology in the blastocyst. We quantified those changes and found that there is an observable spreading of the epiblast and PE tissue in both the MLkb1+/- and MZLkb1-/-) mouse embryos. Taken together, I conclude that Lkb1 does play a role in the early stages of development of the mouse embryos where it affects cell morphology and lineage specification.
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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) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".