Yap and Taz promote osteogenesis in neural crest cells by preventing chondrogenesis

• DOI: 10.1096/fasebj.2022.36.s1.r4623
• Publication Date: 2022-05-03T09:15:06Z
• Authors: Xiaolei Zhao; Li Tang; Bao H. Nguyen; Tram P. Le; Wen Chen; Mingjie Zheng; Hiroyuki Yamaguchi; Idaliz M. Martine...; Jianxin Wang; Min Li; James F. Martin; Brendan H. Lee; Yoshihiro Komatsu; Jun Wang
• Keywords: Chondrogenesis; Hippo signaling pathway; RUNX2

The neural crest (NC) is a unique migratory stem cell population only existed during vertebrate embryogenesis. It has remarkable multipotency to give rise various types including osteoblasts and chondrocytes, which contribute majority of the cranial skeleton development. Defects in NC development led many congenital diseases, cleft palate craniofacial abnormities. Recently, Hippo-Yap pathway, conserved fundamental pathway been indicated play key role NCCs. Yet, roles Yap Taz, function as Hippo signaling effectors, NCC cells are still poorly understood. To understand we performed both vitro, ex vivo studies using O9-1 Yap/Taz conditionally knockout (CKO) mice driven by Wnt1creSOR. We found that required for osteogenic versus chondrogenic fate decision cells. prevent from differentiating into chondrocytes favor osteogenesis, deficiency resulted chondrogenesis instead osteogenesis. Notably, vivo, observed NC-derived bone defects accompanied ectopic cartilage formation. From RNA-seq CUT/RUN datasets directly regulate genes govern osteogenesis (Dlx5, Runx2,…) (Sox9/5/6,…). Interestingly, those known Wnt target genes. Moreover, our data ATAC-seq, PLA Co-IP demonstrated interact with β-catenin coordinately related expression NCCs orchestrate or fate, such gene Sox9. In summary, pivotal determining NC, partly through interactions Wnt-β-catenin reveal potential novel diagnostic therapeutic targets diseases.