Yap/Taz transcriptional activity in endothelial cells promotes intramembranous ossification via the BMP pathway.
Osteogenesis is categorized into two groups based on developmental histology, intramembranous and endochondral ossification. The role of blood vessels during endochondral ossification is well known, while their role in intramembranous ossification, especially the intertissue pathway, is poorly understood. Here, we demonstrate endothelial Yap/Taz is a novel regulator of intramembranous ossification in zebrafish. Appropriate blood flow is required for Yap/Taz transcriptional activation in endothelial cells and intramembranous ossification. Additionally, Yap/Taz transcriptional activity in endothelial cells specifically promotes intramembranous ossification. BMP expression by Yap/Taz transactivation in endothelial cells is also identified as a bridging factor between blood vessels and intramembranous ossification. Furthermore, the expression of Runx2 in pre-osteoblast cells is a downstream target of Yap/Taz transcriptional activity in endothelial cells. Our results provide novel insight into the relationship between blood flow and ossification by demonstrating intertissue regulation.
Laboratory of Function and Morphology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1 Bunkyo-ku, Tokyo, 113-0032 Japan.
Mami
M
Uemura
Laboratory of Function and Morphology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1 Bunkyo-ku, Tokyo, 113-0032 Japan.
Ayumi
A
Nagasawa
Laboratory of Function and Morphology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Yayoi 1-1-1 Bunkyo-ku, Tokyo, 113-0032 Japan.
Kenta
K
Terai
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D010012:Osteogenesis; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015027:Zebrafish
D019485:Bone Morphogenetic Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D014157:Transcription Factors