Mitsiadis T A, Henrique D, Thesleff I, Lendahl U
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden.
Development. 1997 Apr;124(8):1473-83. doi: 10.1242/dev.124.8.1473.
Serrate-like genes encode transmembrane ligands to Notch receptors and control cell fate decisions during development. In this report, we analyse the regulation of the mouse Serrate-1 gene during embryogenesis. The Serrate-1 gene is expressed from embryonic day 7.5 (E7.5) and expression is often observed at sites of epithelial-mesenchymal interactions, including the developing tooth, where Serrate-1 is first (E11.5) expressed in all cells of the dental epithelium, but not in mesenchyme. A transient upregulation in dental mesenchyme (E12.5-15.5) is correlated with down-regulation of Serrate-1 expression in epithelial cells contacting the mesenchyme, i.e. in the cells destined to become ameloblasts. This expression pattern is reproduced in explants of dental epithelium and mesenchyme in vitro: epithelium induces Serrate-1 expression in mesenchyme, while epithelium in close proximity to this mesenchyme does not express detectable levels of Serrate-1 mRNA, suggesting that down-regulation of Serrate-1 expression in preameloblasts is caused by mesenchyme-derived signals. Finally, regulation of Serrate-1 expression differs from that of Notch genes. The Serrate-1 gene is induced in dental mesenchyme by fibroblast growth factor-4, but not by bone morphogenetic proteins, while the converse is true for Notch genes. This indicates that, at least during tooth development, the expression patterns observed for receptors and ligands in the Notch signaling pathway are generated by different induction mechanisms.
锯齿状基因编码Notch受体的跨膜配体，并在发育过程中控制细胞命运决定。在本报告中，我们分析了胚胎发育过程中小鼠锯齿状-1基因的调控。锯齿状-1基因从胚胎第7.5天（E7.5）开始表达，并且常在上皮-间充质相互作用的部位观察到表达，包括发育中的牙齿，在那里锯齿状-1首先（E11.5）在牙上皮的所有细胞中表达，但不在间充质中表达。牙间充质中的短暂上调（E12.5 - 15.5）与接触间充质的上皮细胞中锯齿状-1表达的下调相关，即注定成为成釉细胞的细胞中。这种表达模式在体外牙上皮和间充质外植体中得以重现：上皮诱导间充质中锯齿状-1的表达，但与此间充质紧密相邻的上皮不表达可检测水平的锯齿状-1 mRNA，这表明成釉细胞前体细胞中锯齿状-1表达的下调是由间充质衍生的信号引起的。最后，锯齿状-1表达的调控与Notch基因不同。成纤维细胞生长因子-4可诱导牙间充质中锯齿状-1基因的表达，但骨形态发生蛋白则不能，而Notch基因的情况则相反。这表明，至少在牙齿发育过程中，Notch信号通路中受体和配体的表达模式是由不同的诱导机制产生的。
