PUBLICATION
Yap induces osteoblast differentiation by modulating Bmp signalling during zebrafish caudal fin regeneration
- Authors
- Brandão, A.S., Bensimon-Brito, A., Lourenço, R., Borbinha, J., Soares, A.R., Jacinto, A.
- ID
- ZDB-PUB-191023-6
- Date
- 2019
- Source
- Journal of Cell Science 132(22): (Journal)
- Registered Authors
- Bensimon-Brito, Anabela, Lourenço, Raquel
- Keywords
- Bone, Hippo pathway, Osteoblast, Paracrine signalling, Regeneration
- MeSH Terms
-
- Animal Fins/metabolism
- Animal Fins/physiology*
- Animals
- Bone Morphogenetic Proteins/genetics*
- Cell Differentiation/physiology
- Cell Proliferation
- Osteoblasts/cytology
- Osteoblasts/metabolism*
- Osteogenesis
- Protein Serine-Threonine Kinases/metabolism
- Regeneration/physiology*
- Signal Transduction
- Trans-Activators/antagonists & inhibitors
- Trans-Activators/metabolism*
- Zebrafish/physiology*
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/metabolism*
- PubMed
- 31636113 Full text @ J. Cell Sci.
Citation
Brandão, A.S., Bensimon-Brito, A., Lourenço, R., Borbinha, J., Soares, A.R., Jacinto, A. (2019) Yap induces osteoblast differentiation by modulating Bmp signalling during zebrafish caudal fin regeneration. Journal of Cell Science. 132(22):.
Abstract
Osteoblast differentiation is a key process for bone homeostasis and repair. Multiple signalling pathways have been associated with osteoblast differentiation, yet much remains unknown on how this process is regulated in vivo Previous studies have proposed that the Hippo pathway transcriptional co-activators YAP and TAZ maintain progenitor stemness and inhibit terminal differentiation of osteoblasts, whereas others suggest they potentiate osteoblast differentiation and bone formation. Here, we use zebrafish caudal fin regeneration as a model to clarify how the Hippo pathway regulates de novo bone formation and osteoblast differentiation. We demonstrate that Yap inhibition leads to accumulation of osteoprogenitors and prevents osteoblast differentiation in a cell non-autonomous manner. This effect correlates with a severe impairment of Bmp signalling in osteoblasts, likely by suppressing the expression of the ligand bmp2a in the surrounding mesenchymal cells. Overall, our findings provide a new mechanism of bone formation through the Hippo-Yap pathway, integrating Yap in the signalling cascade that governs osteoprogenitor maintenance and subsequent differentiation during zebrafish caudal fin regeneration.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping