Cowden John, Levine Michael
Department of Molecular and Cell Biology, Division of Genetics and Development, 401 Barker Hall, University of California, Berkeley, CA 94720, USA.
Development. 2002 Apr;129(7):1785-93. doi: 10.1242/dev.129.7.1785.
The maternal Dorsal nuclear gradient initiates the differentiation of the mesoderm, neurogenic ectoderm and dorsal ectoderm in the precellular Drosophila embryo. Each tissue is subsequently subdivided into multiple cell types during gastrulation. We have investigated the formation of the mesectoderm within the ventral-most region of the neurogenic ectoderm. Previous studies suggest that the Dorsal gradient works in concert with Notch signaling to specify the mesectoderm through the activation of the regulatory gene sim within single lines of cells that straddle the presumptive mesoderm. This model was confirmed by misexpressing a constitutively activated form of the Notch receptor, Notch(IC), in transgenic embryos using the eve stripe2 enhancer. The Notch(IC) stripe induces ectopic expression of sim in the neurogenic ectoderm where there are low levels of the Dorsal gradient. sim is not activated in the ventral mesoderm, due to inhibition by the localized zinc-finger Snail repressor, which is selectively expressed in the ventral mesoderm. Additional studies suggest that the Snail repressor can also stimulate Notch signaling. A stripe2-snail transgene appears to induce Notch signaling in 'naïve' embryos that contain low uniform levels of Dorsal. We suggest that these dual activities of Snail, repression of Notch target genes and stimulation of Notch signaling, help define precise lines of sim expression within the neurogenic ectoderm.
母体背核梯度启动了果蝇细胞前期胚胎中中胚层、神经外胚层和背外胚层的分化。在原肠胚形成过程中，每个组织随后被细分为多种细胞类型。我们研究了神经外胚层最腹侧区域中中胚层外胚层的形成。先前的研究表明，背核梯度与Notch信号协同作用，通过激活跨越预定中胚层的单细胞系中的调节基因sim来确定中胚层外胚层。使用eve条纹2增强子在转基因胚胎中错误表达组成型激活形式的Notch受体Notch(IC)，证实了该模型。Notch(IC)条纹在背核梯度水平较低的神经外胚层中诱导sim的异位表达。由于局部锌指蛋白Snail阻遏物的抑制作用，sim在腹侧中胚层中未被激活，Snail阻遏物在腹侧中胚层中选择性表达。进一步的研究表明，Snail阻遏物也可以刺激Notch信号。条纹2-蜗牛转基因似乎在含有低水平均匀背核的“幼稚”胚胎中诱导Notch信号。我们认为，Snail的这些双重作用，即抑制Notch靶基因和刺激Notch信号，有助于在神经外胚层中确定sim表达的精确界限。
