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Record W2978358810 · doi:10.1242/dev.180430

<i>Lats1</i> and <i>Lats2</i> are required for the maintenance of multipotency in the Müllerian duct mesenchyme

2019· article· en· W2978358810 on OpenAlexafffund
Guillaume St‐Jean, Mayra Tsoi, Atefeh Abedini, Adrien Levasseur, Charlène Rico, Martin Morin, Bojana Djordjevic, Ilkka Miinalainen, Riitta Kaarteenaho, Marilène Paquet, Nicolas Gévry, Alexandre Boyer, Barbara C. Vanderhyden, Derek Boerboom

Bibliographic record

VenueDevelopment · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHippo pathway signaling and YAP/TAZ
Canadian institutionsHealth Sciences CentreSunnybrook Health Science CentreUniversity of OttawaUniversité de SherbrookeUniversité de Montréal
FundersCanadian Institutes of Health Research
KeywordsBiologyHippo signaling pathwayMesenchymeCell biologyWnt signaling pathwayMesodermIntermediate mesodermYAP1MyofibroblastMesenchymal stem cellSignal transductionGeneticsInternal medicineEmbryonic stem cellEmbryoTranscription factorEmbryogenesisFibrosis

Abstract

fetched live from OpenAlex

WNT signaling plays essential roles in the development and function of the female reproductive tract. Although crosstalk with the Hippo pathway is a key regulator of WNT signaling, whether Hippo itself plays a role in female reproductive biology remains largely unknown. In this report, we show that conditional deletion of the key Hippo kinases Lats1 and Lats2 in Müllerian duct mesenchyme cells caused them to adopt the myofibroblast cell fate, resulting in profound reproductive tract developmental defects and sterility. Myofibroblast differentiation was attributed to increased YAP and TAZ expression (but not to altered WNT signaling), leading to the direct transcriptional up-regulation of Ctgf and the activation of the myofibroblast genetic program. Müllerian duct mesenchyme cells also became myofibroblasts in male mutant embryos, which impeded the development of the male reproductive tract and resulted in cryptorchidism. The inactivation of Lats1/2 in differentiated uterine stromal cells in vitro did not compromise their ability to decidualize, suggesting that Hippo is dispensable during implantation. We conclude that Hippo signaling is required to suppress the myofibroblast genetic program and maintain multipotency in Müllerian mesenchyme cells.

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)0.001
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 score0.468
Threshold uncertainty score0.279

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 head0.013
GPT teacher head0.227
Teacher spread0.214 · 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
Published2019
Admission routes2
Has abstractyes

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