Barrantes I B, Elia A J, Wünsch K, Hrabe de Angelis M H, Mak T W, Rossant J, Conlon R A, Gossler A, de la Pompa J L
Amgen Institute, Ontario Cancer Institute, Departments of Medical Biophysics and Immunology University of Toronto 620 University Avenue, Toronto, Ontario, M5G 2C1, Canada.
Curr Biol. 1999 May 6;9(9):470-80. doi: 10.1016/s0960-9822(99)80212-7.
The process of somitogenesis can be divided into three major events: the prepatterning of the mesoderm; the formation of boundaries between the prospective somites; and the cellular differentiation of the somites. Expression and functional studies have demonstrated the involvement of the murine Notch pathway in somitogenesis, although its precise role in this process is not yet well understood. We examined the effect of mutations in the Notch pathway elements Delta like 1 (Dll1), Notch1 and RBPJkappa on genes expressed in the presomitic mesoderm (PSM) and have defined the spatial relationships of Notch pathway gene expression in this region.
We have shown that expression of Notch pathway genes in the PSM overlaps in the region where the boundary between the posterior and anterior halves of two consecutive somites will form. The Dll1, Notch1 and RBPJkappa mutations disrupt the expression of Lunatic fringe (L-fng), Jagged1, Mesp1, Mesp2 and Hes5 in the PSM. Furthermore, expression of EphA4, mCer 1 and uncx4.1, markers for the anterior-posterior subdivisions of the somites, is down-regulated to different extents in Notch pathway mutants, indicating a global alteration of pattern in the PSM.
We propose a model for the mechanism of somite border formation in which the activity of Notch in the PSM is restricted by L-fng to a boundary-forming territory in the posterior half of the prospective somite. In this region, Notch function activates a set of genes that are involved in boundary formation and anterior-posterior somite identity.
体节发生过程可分为三个主要事件：中胚层的预模式形成；预期体节之间边界的形成；以及体节的细胞分化。表达和功能研究已证明小鼠Notch信号通路参与体节发生，尽管其在这一过程中的精确作用尚未完全明确。我们研究了Notch信号通路元件Delta样1（Dll1）、Notch1和RBPJκ的突变对原肠胚中胚层（PSM）中表达基因的影响，并确定了该区域Notch信号通路基因表达的空间关系。
我们发现，PSM中Notch信号通路基因的表达在两个连续体节前后半部分之间的边界将要形成的区域重叠。Dll1、Notch1和RBPJκ的突变破坏了PSM中 Lunatic fringe（L-fng）、Jagged1、Mesp1、Mesp2和Hes5的表达。此外，体节前后分区标记物EphA4、mCer 1和uncx4.1在Notch信号通路突变体中的表达不同程度下调，表明PSM中的模式发生了全局性改变。
我们提出了一个体节边界形成机制的模型，其中PSM中Notch的活性被L-fng限制在预期体节后半部分的一个边界形成区域。在这个区域，Notch功能激活一组参与边界形成和体节前后身份确定的基因。
