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Record W4393216241 · doi:10.1016/j.celrep.2024.114005

Pten regulates endocytic trafficking of cell adhesion and Wnt signaling molecules to pattern the retina

2024· article· en· W4393216241 on OpenAlexafffund
Yacine Touahri, Joseph Hanna, Nobuhiko Tachibana, Satoshi Okawa, Hedy Liu, Luke Ajay David, Thomas Olender, Lakshmy Vasan, Alissa Pak, Dhruv Nimesh Mehta, Vorapin Chinchalongporn, Anjali Balakrishnan, Robert Cantrup, Rajiv Dixit, Pierre Mattar, Fermisk Saleh, Yaroslav Ilnytskyy, Monzur Murshed, Paul E. Mains, Igor Kovalchuk, Julie L. Lefebvre, Hon S. Leong, Michel Cayouette, Chao Wang, Antonio del Sol, Marjorie Brand, Benjamin E. Reese, Carol Schuurmans

Bibliographic record

VenueCell Reports · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCellular transport and secretion
Canadian institutionsHospital for Sick ChildrenMontreal Clinical Research InstituteUniversity of LethbridgeOttawa HospitalUniversity of OttawaMcGill UniversityUniversity of CalgaryUniversity of TorontoAlberta Children's HospitalSunnybrook Health Science Centre
FundersNational Eye InstituteAlberta Children's Hospital Research InstituteNational Institutes of HealthCanadian Institutes of Health ResearchSunnybrook Research InstituteUniversity of Washington
KeywordsEndocytic cycleCell biologyWnt signaling pathwayRetinaPTENCell adhesion moleculeCell adhesionCell signalingSignal transductionBiologyCellChemistryEndocytosisNeurosciencePI3K/AKT/mTOR pathwayGenetics

Abstract

fetched live from OpenAlex

The retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog ( P ten ) controls starburst amacrine cell spacing by modulating vesicular trafficking of cell adhesion molecules and Wnt proteins. Single-cell transcriptomics and double-mutant analyses revealed that Pten and Down syndrome cell adhesion molecule Dscam ) are co-expressed and function additively to pattern starburst amacrine cell mosaics. Mechanistically, Pten loss accelerates the endocytic trafficking of DSCAM, FAT3, and MEGF10 off the cell membrane and into endocytic vesicles in amacrine cells. Accordingly, the vesicular proteome, a molecular signature of the cell of origin, is enriched in exocytosis, vesicle-mediated transport, and receptor internalization proteins in Pten conditional knockout ( Pten cKO ) retinas. Wnt signaling molecules are also enriched in Pten cKO retinal vesicles, and the genetic or pharmacological disruption of Wnt signaling phenocopies amacrine cell patterning defects. Pten thus controls vesicular trafficking of cell adhesion and signaling molecules to establish retinal amacrine cell mosaics.

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.381

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.007
GPT teacher head0.207
Teacher spread0.200 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations15
Published2024
Admission routes2
Has abstractyes

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