Stump Gila, Durrer André, Klein Anne-Laurence, Lütolf Simone, Suter Ueli, Taylor Verdon
Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
Mech Dev. 2002 Jun;114(1-2):153-9. doi: 10.1016/s0925-4773(02)00043-6.
Notch signaling plays a pivotal role in the regulation of vertebrate neurogenesis. However, in vitro experiments suggest that Notch1 may also be involved in the regulation of later stages of brain development. We have addressed putative roles in the central nervous system by examining the expression of Notch signaling cascade components in the postnatal mouse brain. In situ mRNA hybridization revealed that Notch1 is associated with cells in the subventricular zone, the dentate gyrus and the rostromigratory stream, all regions of continued neurogenesis in the postnatal brain. In addition, Notch1 is expressed at low levels throughout the cortex and olfactory bulb and shows striking expression in the cerebellar Purkinje cell layer. The Notch ligands, including Delta-like1 and 3 and Jagged1 and Jagged2, show distinct expression patterns in the developing and adult brain overlapping that of Notch1. In addition, the downstream targets of the Notch signaling cascade Hes1, Hes3, Hes5 and the intrinsic Notch regulatory proteins Numb and Numblike also show active signaling in distinct brain regions. Hes5 coincides with the majority of Notch1 expression and can be detected in the cerebral cortex, cerebellum and putative germinal zones. Hes3, on the other hand, shows a restricted expression in cerebellar Purkinje cells. The distribution of Notch1 and its putative ligands suggest distinct roles in specific subsets of cells in the postnatal brain including putative stem cells and differentiated neurons.
Notch信号通路在脊椎动物神经发生的调控中起关键作用。然而,体外实验表明Notch1可能也参与脑发育后期阶段的调控。我们通过检测Notch信号级联成分在出生后小鼠脑中的表达,探讨了其在中枢神经系统中的假定作用。原位mRNA杂交显示,Notch1与脑室下区、齿状回和吻侧迁移流中的细胞相关,这些都是出生后脑内持续发生神经发生的区域。此外,Notch1在整个皮质和嗅球中低水平表达,并在小脑浦肯野细胞层中呈现显著表达。Notch配体,包括Delta样1和3以及锯齿状蛋白1和2,在发育中和成年脑中呈现出与Notch1重叠的独特表达模式。此外,Notch信号级联的下游靶点Hes1、Hes3、Hes5以及内在的Notch调节蛋白Numb和Numblike在不同脑区也显示出活跃的信号传导。Hes5与大多数Notch1表达区域一致,可在大脑皮质、小脑和假定的生发区中检测到。另一方面,Hes3在小脑浦肯野细胞中呈现局限性表达。Notch1及其假定配体的分布表明它们在出生后脑内特定细胞亚群中具有不同作用,包括假定的干细胞和分化神经元。