PUBLICATION
The TET-Sall4-BMP regulatory axis controls craniofacial cartilage development
- Authors
- Wang, W., Yang, N., Wang, L., Zhu, Y., Chu, X., Xu, W., Li, Y., Xu, Y., Gao, L., Zhang, B., Zhang, G., Sun, Q., Wang, W., Wang, Q., Zhang, W., Chen, D.
- ID
- ZDB-PUB-240302-2
- Date
- 2024
- Source
- Cell Reports 43: 113873113873 (Journal)
- Registered Authors
- Wang, Qiang
- Keywords
- CP: Developmental biology, CP: Molecular biology
- Datasets
- GEO:GSE226184
- MeSH Terms
-
- Animals
- Cartilage*/metabolism
- Cell Differentiation/genetics
- Chondrogenesis/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 38427557 Full text @ Cell Rep.
Citation
Wang, W., Yang, N., Wang, L., Zhu, Y., Chu, X., Xu, W., Li, Y., Xu, Y., Gao, L., Zhang, B., Zhang, G., Sun, Q., Wang, W., Wang, Q., Zhang, W., Chen, D. (2024) The TET-Sall4-BMP regulatory axis controls craniofacial cartilage development. Cell Reports. 43:113873113873.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping