Open AccessYap induces osteoblast differentiation by modulating Bmp signalling during zebrafish caudal fin regeneration
Author(s) -
Ana S. Brandão,
Anabela Bensimon-Brito,
Raquel Lourenço,
Jorge Borbinha,
Amílcar Soares,
Rita Mateus,
António Jacinto
Publication year - 2019
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.231993
Subject(s) - zebrafish , biology , osteoblast , microbiology and biotechnology , hippo signaling pathway , regeneration (biology) , cellular differentiation , mesenchymal stem cell , bone morphogenetic protein , progenitor cell , bone morphogenetic protein 2 , signal transduction , stem cell , genetics , gene , in vitro
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.