[P2.29]: Role of alternatively spliced disabled‐1 in developing retina
Bibliographic record
Abstract
The Reelin-disabled-1 (Dab1) signaling pathway plays key roles in neuronal positioning in the developing central nervous system. Binding of Reelin to its receptors induces Dab1 tyrosine phosphorylation and stimulates Src family kinases (SFK) activation. phosphorylated Dab1 relays the signal to downstream molecules, leading to the proper layering of neurons in the developing brain. We have identified two alternatively spliced forms of Dab1 in the developing retina: an early form (Dab1-E), expressed in undifferentiated retinal progenitor cells at early stages, and a late form (Dab1-L, referred to as Dab1 in the literature), expressed in differentiated ganglion and amacrine cells at late developmental stages. A major difference between these two isoforms is the exclusion of two SFK recognition motifs from Dab1-E. Moreover, Dab1-L is tyrosine phosphorylated, whereas Dab1-E is serine/threonine phosphorylated. Transfection of Dab1-E and Dab1-L expression constructs into Reelin-responsive primary retinal cultures induces distinct effects including different cellular morphology, differential tyrosine phosphorylation and SFK activation. The distinct expression and phosphorylation profile of Dab1-E and Dab1-L in the developing retina, combined with the different morphology observed upon expression of Dab1-E and Dab1-L into retinal cultures suggest a novel paradigm for the regulation of Dab1 function. To further characterize the role of Dab1 isoforms, we are using kinase inhibitors and kinase assays to identify kinases involved in Dab1-E phosphorylation. As well, we are using the avian retrovirus-based RNA interference system to specifically knockdown the levels of Dab1-E and Dab1-L at different developmental stages of chick retina. We will determine the consequences of reducing Dab1-E and Dab1-L levels in the developing retina and investigate the downstream effectors of Dab1 using this model system.
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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 | 0.001 | 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".