CNTD1 plays crucial roles in prophase I progression and crossover designation during female meiosis and is critical for establishing the ovarian reserve
Bibliographic record
Abstract
ABSTRACT In meiotic prophase I, hundreds of double-strand breaks (DSBs) are formed throughout the genome. A majority of these breaks are repaired as non-crossovers (NCOs), while a minor subset are repaired as crossovers (CO). COs are essential for the faithful segregation of homologous chromsomes at the end of prophase I and errors in CO designation can result in aneuploidy, germ cell death, birth defects, or infertility. These errors are more evident in female meiosis compared to males and suggests that the events of meiotic prophase I are sexually dimorphic with respect to CO formation, placement, resolution, and/or surveillance. Here, we demonstrate a critical role for Cyclin N-Terminal Domain Containing 1 (CNTD1) protein in ensuring appropriate CO frequency and distribution across the genome during meiosis in females. We find that CNTD1 localizes with the heterodimer, MutLγ, which marks the majority of CO that emerge in pachynema of prophase I, implicating CNTD1 in late-stage CO designation and/or maturation. Accordingly, loss of Cntd1 in oocytes results in failure to load MutLγ and thus results in a catastrophic loss of chiasmata and sterility. Further investigation yielded a distinct phenotype in which the primordial follicles that form upon dictyate arrest are steadily lost from birth onwards, a temporal loss of follicles that is different to that seen in other CO mutants. We find that this follicle loss in Cntd1 mutants is dependent on the checkpoint kinase CHK2. Thus, in females, loss of Cntd1 appears to result in phenotypes that are temporally disconnected from early and late CO mutants such as MutSγ and MutLγ, which show early prophase I disruption and ablation of ovary structure, and no prophase I disruption and an appearance of wildtype ovaries, respectively. These data suggest novel dual roles for CNTD1 in CO designation and faithful progression of oocytes into dictyate arrest at late pachynema, the latter being critical for establishing the ovarian reserve in female mice.
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) | 0.000 | 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) | 0.002 | 0.001 |
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".