nkx2.3 is responsible for posterior pharyngeal cartilage formation by inhibiting Fgf signaling
Shuyan Yang,
Xin Xu,
Zheng Yin,
Yuelin Liu,
Handong Wang,
Jin Guo,
Fang Wang,
Yihua Bao,
Ting Zhang,
Shaoguang Sun
Affiliations
Shuyan Yang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China; Corresponding author.
Xin Xu
Department of Biochemistry and Molecular Biology, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710054, China
Zheng Yin
Department of Biochemistry and Molecular Biology, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang, Hebei, 050017, China
Yuelin Liu
Department of Biochemistry and Molecular Biology, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang, Hebei, 050017, China
Handong Wang
Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China
Jin Guo
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China
Fang Wang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China
Yihua Bao
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China
Ting Zhang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China
Shaoguang Sun
Department of Biochemistry and Molecular Biology, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Corresponding author.
Nkx2.3, a transcription factor, plays important roles in various developmental processes. However, the mechanisms underlying nkx2.3's regulation of pouch and pharyngeal arch development in zebrafish remain unclear. In this study, we demonstrated that knockdown or knockout of nkx2.3 resulted in the absence of posterior ceratobranchial cartilages in zebrafish. The absence of posterior pharyngeal cartilages is a consequence of the compromised proliferation and differentiation and survival of cranial neural crest cells (CNCCs). Notably, we found that nkx2.3 was not involved in endoderm pouch formation. Additionally, our findings suggested that nkx2.3 negatively regulated Fibroblast growth factor (Fgf) signaling, as overexpression of fgf8 could mimic the phenotype observed in nkx2.3 morphants, suppressing CNCC differentiation. Moreover, inhibiting Fgf signaling restored the abnormalities in posterior cartilages induced by nkx2.3 knockdown. These findings establish the essential role of nkx2.3 in the development of posterior ceratobranchial cartilages through the inhibition of fgf8.
