Hippo Signaling Is Essential for the Maintenance of Zona Glomerulosa Cell Fate in the Murine Adrenal Cortex
Bibliographic record
Abstract
Cells of the zona glomerulosa (zG), the outermost zone of the adrenal cortex, secrete aldosterone and transdifferentiate into glucocorticoid-producing cells of the zona fasciculata (zF) during adrenal homeostasis. However, our understanding of the signaling pathways mediating zG cell maintenance or their transdifferentiation into zF cells is incomplete. Hippo is a major pathway that regulates cell proliferation/differentiation during embryogenesis and postnatal tissue homeostasis. Hypothesizing that Hippo signaling could be involved in zG cell maintenance or transdifferentiation, we generated a mouse model in which the two main kinases of the Hippo signaling cascade large tumor suppressor homolog kinases 1/2 (Lats1 and Lats2) are specifically inactivated in zG cells. Here we show that loss of function of Lats1 and Lats2 impairs zG steroidogenesis and leads to zG cell transdifferentiation into cells sharing characteristics with chondroblasts/osteoblasts rather than zF cells. Furthermore, we demonstrate that this phenotype can be rescued by the concomitant inactivation of the transcriptional coactivators Yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) with Lats1 and Lats2. Finally, we show that expression of a constitutively active form of YAP (YAP5SA) in zG cells does not alter their fate as severely as the loss of Lats1 and Lats2 but leads to adrenal hyperplasia. Together, these findings highlight the critical role of Hippo signaling in maintaining zG cell fate and function and provide key insights into broader mechanisms underlying cellular differentiation.
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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) | 0.001 | 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 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".