Myoneurin regulates BMP signaling by competing with Ppm1a for Smad binding
Shuyan Yang,
Guozhu Ning,
Yiming Hou,
Yu Cao,
Jin Xu,
Jianxin Wu,
Ting Zhang,
Qiang Wang
Affiliations
Shuyan Yang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China
Guozhu Ning
Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou 510006, China; State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China
Yiming Hou
State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China
Yu Cao
State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China
Jin Xu
Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou 510006, China
Jianxin Wu
Beijing TongRen Hospital, Capital Medical University, 17 Hougou Street, Chong Wen Men, Beijing 100005, PR China; Corresponding author
Ting Zhang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China; Corresponding author
Qiang Wang
Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou 510006, China; State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China; Corresponding author
Summary: A delicate balance of BMP activity is critical for tissue formation and organogenesis. However, the mechanical molecular details in ensuring the proper duration and intensity of BMP signaling have yet to be fully elucidated. Here, we identified a zebrafish mutant with a disrupted gene encoding for the BTB/POZ and zinc finger protein myoneurin (Mynn). mynn−/− mutants exhibited severe loss of pharyngeal cartilage elements, owing to poor proliferation, blocked differentiation, and low viability of cranial neural crest cells. Depletion of mynn in both zebrafish embryos and mammalian cells led to a reduction of the BMP signal activity. Mechanistically, Mynn interacts with Smad proteins in the nucleus, thereby disrupting the association between Smad protein and the phosphatase Ppm1a. Ultimately, this interaction prevents Smad dephosphorylation. More broadly, our findings may provide a new strategy to balance BMP signal activity via competitive binding of Mynn and Ppm1a to Smad proteins during pharyngeal cartilage formation.
