Nr2e1 regulates retinal lamination and the development of Müller glia, S-cones, and glycineric amacrine cells during retinogenesis
Bibliographic record
Abstract
BACKGROUND: Nr2e1 is a nuclear receptor crucial for neural stem cell proliferation and maintenance. In the retina, lack of Nr2e1 results in premature neurogenesis, aberrant blood vessel formation and dystrophy. However, the specific role of Nr2e1 in the development of different retinal cell types and its cell-autonomous and non-cell autonomous function(s) during eye development are poorly understood. RESULTS: Here, we studied the retinas of P7 and P21 Nr2e1 (frc/frc) mice and Nr2e1 (+/+) ↔ Nr2e1 (frc/frc) chimeras. We hypothesized that Nr2e1 differentially regulates the development of various retinal cell types, and thus the cellular composition of Nr2e1 (frc/frc) retinas does not simply reflect an overrepresentation of cells born early and underrepresentation of cells born later as a consequence of premature neurogenesis. In agreement with our hypothesis, lack of Nr2e1 resulted in increased numbers of glycinergic amacrine cells with no apparent increase in other amacrine sub-types, normal numbers of Müller glia, the last cell-type to be generated, and increased numbers of Nr2e1 (frc/frc) S-cones in chimeras. Furthermore, Nr2e1 (frc/frc) Müller glia were mispositioned in the retina and misexpressed the ganglion cell-specific transcription factor Brn3a. Nr2e1 (frc/frc) retinas also displayed lamination defects including an ectopic neuropil forming an additional inner plexiform layer. In chimeric mice, retinal thickness was rescued by 34 % of wild-type cells and Nr2e1 (frc/frc) dystrophy-related phenotypes were no longer evident. However, the formation of an ectopic neuropil, misexpression of Brn3a in Müller glia, and abnormal cell numbers in the inner and outer nuclear layers at P7 were not rescued by wild-type cells. CONCLUSIONS: Together, these results show that Nr2e1, in addition to having a role in preventing premature cell cycle exit, participates in several other developmental processes during retinogenesis including neurite organization in the inner retina and development of glycinergic amacrine cells, S-cones, and Müller glia. Nr2e1 also regulates various aspects of Müller glia differentiation cell-autonomously. However, Nr2e1 does not have a cell-autonomous role in preventing retinal dystrophy. Thus, Nr2e1 regulates processes involved in neurite development and terminal retinal cell differentiation.
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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".