10Wnt与Notch信号传导(正式).ppt

* 细胞迁移、细胞骨架调节，染色体分离等 * 除甲状腺素 * * * β- 连环蛋白被GSK-3β磷酸化后，就被泛素化，最终被蛋白酶体降解 * During normal gastrulation, lateral cells migrate towards the midline, intercalating between one another and thus lengthening the embryo along the anterior–posterior axis ( * (a) The establishment of planar polarity throughout the wing of Drosophila relies upon the upstream components of the Wingless signaling pathway. Both Frizzled and Dishevelled are required to orient the actin-based hairs protruding from the distal-most vertex of each wing cell. In their absence, the proximal–distal orientation of the wing hairs is disrupted. (b) Two distinct pathways function downstream of Frizzled and Dishevelled. Stabilization of Armadillo in the cytoplasm depends on the canonical Wingless signaling pathway, which includes Zeste white-3, dAPC/2 and dAXIN, and results in transcriptional activation by dTCF and Armadillo. The regulation of planar cell polarity depends on a distinct set of intracellular effectors, including the JNK signaling cascade. Such effectors are thought to affect planar cell polarity by regulating the cytoskeleton directly as well as gene transcription independent of Armadillo/β-catenin. (c) Convergent extension is the process whereby mesodermal cells intercalate and thereby lengthen the embryo along the anterior–posterior axis. Recent work by Heisenberg et al. [6], Wallingford et al. [7] and Tada and Smith [8] has shown that the regulation of convergent extension depends on the planar-cell polarity pathway downstream of the DEP domain of Dishevelled (see text for details).  * * 存在于细胞质膜上的受体， * * 与βγ 亚基分离 * 3. Wnt/Ca2+通路 ? 最初证据来源于斑马鱼和爪蟾的研究 ? Wnt-5A能刺激细胞内Ca2+的释放 ? 有Frizzled-2(Rfz-2)参与 ? Ca2+激活CaMKⅡ和PKC (二) Wnt信号与胚胎体轴和中胚层模式的建立 体轴的形成需要β- 连环蛋白以及Wnt/ β- 连环蛋白通路信号分子参与。 ? 背前侧β- 连环蛋白的聚集 — 最早标志 ? β- 连环蛋白的过表达，可诱导胚胎产生额外体轴。 ? β- 连环蛋白调节的典型Wnt信号参与前后轴的形成 ? β- 连环蛋白敲除的胚胎， 可发生细胞的错误定位，从而不能形成中胚层。 ? 抑制Wnt信号是脊椎动物体廓形成后期阶段的关键因素。 ? Wnt拮抗分子能诱导头的形成。 (三) Wnt信号与器官发生 ★ Wnt信号参与大脑的形成