Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Dev Biol. 2012 Apr 1;364(1):77-87. doi: 10.1016/j.ydbio.2012.01.017. Epub 2012 Jan 27.
In sea urchin embryos Delta signaling specifies non-skeletogenic mesoderm (NSM). Despite the identification of some direct targets, several aspects of Delta Notch (D/N) signaling remain supported only by circumstantial evidence. To obtain a detailed and more complete image of Delta function we followed a systems biology approach and evaluated the effects of D/N perturbation on expression levels of 205 genes up to gastrulation. This gene set includes virtually all transcription factors that are expressed in a localized fashion by mid-gastrulation, and which thus provide spatial regulatory information to the embryo. Also included are signaling factors and some pigment cell differentiation genes. We show that the number of pregastrular D/N signaling targets among these regulatory genes is small and is almost exclusively restricted to non-skeletogenic mesoderm genes. However, Delta signaling also activates foxY in the small micromeres. As is the early NSM, the small micromeres are in direct contact with Delta expressing skeletogenic mesoderm. In contrast, no endoderm regulatory genes are activated by Delta signaling even during the second phase of delta expression, when this gene is transcribed in NSM cells adjacent to the endoderm. During this phase Delta provides an ongoing input which continues to activate foxY expression in small micromere progeny. Disruption of the second phase of Delta expression specifically abolishes specification of late mesodermal derivatives such as the coelomic pouches to which the small micromeres contribute.
在海胆胚胎中，Delta 信号指定非骨骼生成中胚层（NSM）。尽管已经鉴定出一些直接靶标，但 Delta Notch（D/N）信号的几个方面仍然仅由间接证据支持。为了获得 Delta 功能的详细和更完整的图像，我们采用了系统生物学方法，评估了 D/N 扰动对 205 个基因表达水平的影响，直至原肠胚形成。该基因集几乎包括所有在中胚层形成时以局部方式表达的转录因子，因此为胚胎提供了空间调节信息。还包括信号因子和一些色素细胞分化基因。我们表明，这些调节基因中 pregastrular D/N 信号靶标的数量很少，几乎仅局限于非骨骼生成中胚层基因。然而，Delta 信号也在小原细胞中激活 foxY。与早期 NSM 一样，小原细胞与表达骨骼生成中胚层的 Delta 直接接触。相比之下，即使在 delta 表达的第二阶段（当该基因在与内胚层相邻的 NSM 细胞中转录时），Delta 信号也不会激活内胚层调节基因。在这个阶段，Delta 提供了一个持续的输入，继续激活小原细胞后代中 foxY 的表达。第二阶段 Delta 表达的中断特异性地破坏了晚期中胚层衍生物的指定，例如小原细胞贡献的体腔囊。
