Molecular and functional analysis of Notch signaling in organogenesis

Notch信号是一条进化保守的通路，在多种器官的发育过程中发挥着重要作用。本研究以斑马鱼为研究对象，分析了Notch配体的生理功能及其调控机制。我们发现了一种以前未知的机制，通过Mib-Jag1-Notch信号调节脊索的模式和结构角色。此外，通过生化筛选，我们确定了Notch为NLK的新底物。NLK-磷酸化的Notch1胞间结构域形成转录活性三元复合体的能力受到损害。

Notch signaling is an evolutionary conserved pathway that plays an important role in the development of various organs. In this study, physiological functions of Notch ligands and the mechanism by which Notch activity is regulated were analyzed using zebrafish. We found a previously unrecognized mechanism regulating the patterning and structural roles of the notochord by Mib-Jag1-Notch signaling. Furthermore, using a biochemical screen, we identified Notch as a new substrate of NLK. NLK-phosphorylated Notch1 intercellular domain is impaired in its ability to form a transcriptionally active ternary complex.