Molecular and functional analysis of Notch signaling in organogenesis

Notch信号通路是一种进化上保守的信号通路，在各种器官的发育中起着重要作用。在这项研究中，Notch配体的生理功能和Notch活性的调节机制进行了分析，使用斑马鱼。我们发现了一种以前未被认识的机制，通过Mib-Jag 1-Notch信号调节脊索的模式和结构作用。此外，使用生物化学筛选，我们确定Notch为NLK的新底物。NLK-磷酸化Notch 1胞间结构域形成转录活性三元复合物的能力受损。

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.