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Yap and Taz function as the osteochondrogenic determinant in neural crest cells
Author(s) -
Zhao Xiaolei,
Tang Li,
Nguyen Bao,
Le Tram,
Chen Wen,
Zheng Mingjie,
Yamaguchi Hiroyuki,
MartinezTraverso Idaliz,
Martin James,
Wang Jianxin,
Li Min,
Lee Brendan,
Komatsu Yoshihiro,
Wang Jun
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.04713
Subject(s) - microbiology and biotechnology , wnt signaling pathway , biology , chondrogenesis , runx2 , neural crest , chondrocyte , cell fate determination , hippo signaling pathway , transcription factor , stem cell , signal transduction , cartilage , genetics , gene , anatomy , embryo
The neural crest cells (NCCs) are multipotent stem cells making pivotal contributions to many tissues and organs during embryonic development. NCCs have remarkable ability to differentiate into various cell lineages including osteoblasts and chondrocytes, yet it is largely unknown how NCCs make cell fate decisions and differentiate into specific cell lineages. Here we found Yap/Taz are required for NCC‐derived osteoblasts differentiation and notably, Yap/Taz deficiency caused cell fate switch from osteogenic into chondrogenic in vitro . In vivo Yap/Taz specific deletion in NCCs caused cranial bone defects and ectopic cartilage formation in mouse. We have performed a combined analysis of data sets including RNA‐seq and Reverse Phase Protein Array (RPPA) of control and Yap/Taz deficient samples, ATAC‐seq (assay for transposase‐accessible chromatin with high‐throughput sequencing) of human and mouse NCCs, and CUT&RUN (Cleavage Under Targets & Release Using Nuclease)‐seq data using Yap antibody, as well as immunoprecipitation data. We found Yap/Taz directly regulate key genes in osteogenesis and chondrogenesis including Sox9 and Runx2 that control the cell fates of osteoblast and chondrocyte lineages, and other genes such as Sox5, Sox6, and Osx . This regulation is partially through that Yap/Taz interacts with β‐catenin in NCCs and coordinately regulate genes expression at genome‐wide. Together, we demonstrate that Yap/Taz play pivotal roles in NCCs derived cranial bone formation and osteochondrogenic cell fate decision, which partially functions through the interaction with the Wnt‐β‐catenin pathway.