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The TET-Sall4-BMP regulatory axis controls craniofacial cartilage development.
Wang, Weigang; Yang, Na; Wang, Liangliang; Zhu, Yuanxiang; Chu, Xiao; Xu, Weijie; Li, Yawei; Xu, Yihai; Gao, Lina; Zhang, Beibei; Zhang, Guoqiang; Sun, Qinmiao; Wang, Weihong; Wang, Qiang; Zhang, Wenxin; Chen, Dahua.
Afiliación
  • Wang W; Institute of Biomedical Research, Yunnan University, Kunming, China.
  • Yang N; Institute of Biomedical Research, Yunnan University, Kunming, China; Department of Ultrasound, The Second Affiliated Hospital of Kunming Medical University, Kunming, China.
  • Wang L; Institute of Biomedical Research, Yunnan University, Kunming, China.
  • Zhu Y; Institute of Biomedical Research, Yunnan University, Kunming, China.
  • Chu X; Institute of Biomedical Research, Yunnan University, Kunming, China.
  • Xu W; Institute of Biomedical Research, Yunnan University, Kunming, China.
  • Li Y; Institute of Biomedical Research, Yunnan University, Kunming, China.
  • Xu Y; Institute of Biomedical Research, Yunnan University, Kunming, China.
  • Gao L; Institute of Biomedical Research, Yunnan University, Kunming, China.
  • Zhang B; Institute of Biomedical Research, Yunnan University, Kunming, China.
  • Zhang G; Institute of Biomedical Research, Yunnan University, Kunming, China.
  • Sun Q; Institute of Stem Cells and Regeneration, Chinese Academy of Sciences, Beijing, China.
  • Wang W; Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, Kunming, China. Electronic address: wangweihong@kmmu.edu.cn.
  • Wang Q; Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou, China. Electronic address: qiangwang@scut.edu.cn.
  • Zhang W; Institute of Biomedical Research, Yunnan University, Kunming, China. Electronic address: zhangwx@ynu.edu.cn.
  • Chen D; Institute of Biomedical Research, Yunnan University, Kunming, China; Southwest United Graduate School, Kunming, China. Electronic address: chendh@ynu.edu.cn.
Cell Rep ; 43(3): 113873, 2024 Mar 26.
Article en En | MEDLINE | ID: mdl-38427557
ABSTRACT
Craniofacial microsomia (CFM) is a congenital defect that usually results from aberrant development of embryonic pharyngeal arches. However, the molecular basis of CFM pathogenesis is largely unknown. Here, we employ the zebrafish model to investigate mechanisms of CFM pathogenesis. In early embryos, tet2 and tet3 are essential for pharyngeal cartilage development. Single-cell RNA sequencing reveals that loss of Tet2/3 impairs chondrocyte differentiation due to insufficient BMP signaling. Moreover, biochemical and genetic evidence reveals that the sequence-specific 5mC/5hmC-binding protein, Sall4, binds the promoter of bmp4 to activate bmp4 expression and control pharyngeal cartilage development. Mechanistically, Sall4 directs co-phase separation of Tet2/3 with Sall4 to form condensates that mediate 5mC oxidation on the bmp4 promoter, thereby promoting bmp4 expression and enabling sufficient BMP signaling. These findings suggest the TET-BMP-Sall4 regulatory axis is critical for pharyngeal cartilage development. Collectively, our study provides insights into understanding craniofacial development and CFM pathogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Cartílago Límite: Animals Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Cartílago Límite: Animals Idioma: En Revista: Cell Rep Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos