几种重要的信号转导通路PPT课件.ppt

. In the absence of dVps35 activity: Wg protein is accumulated inside Wg-producing cells, but reduced on the cell surface of Wg-producing cells and in surrounding Wg-recieving cells. Wg protein levels are reduced in conditioned medium. Conclusion: Retromer is required for Wg secretion. Question: How Does Retromer regulate Wg secretion ? * Similarity between dvps35 and Wls mutants B A Wg GFP E-cad merge B A Wg GFP E-cad merge B A Wg GFP E-cad merge B A Wg GFP E-cad merge GFP Wg Merge wls Hypothesis: Retromer may control Wg/Wnt secretion by regulating Wls activity * dVps35 interacts with Wls * Morphogen “ A form generating substance that diffuses through a tissue, its distribution dictating the development of cells in the tissue” Alan Turing (1952). The chemical basis of morphogenesis. Philos. Trans. R. Soc. Lond. B Biol. Sci. 237, 37-72 * Growth Factor Morphogens Signaling molecules produced in a restricted regions within a tissue. Morphogens emanate from their source to form a long-range concentration gradient. Receiving cells interpret morphogen gradient by activating target gene expression at discrete concentration thresholds thereby acquiring positional information. Two criteria: 1. Concentration dependence. 2. Direct action at a distance Wnt, Hh, and TGF-β are morphogens. * 形态发生素功能失调相关的人类疾病 前脑无裂畸形 (HPE) 骨发育不良 神经管发育缺陷 肾母细胞瘤 结肠癌 家族性渗出性玻璃体视网膜病变 骨质疏松-假性神经胶质瘤综合症(OPS) 裂足症 先天性四肢切断症 * * Vertebrates: SHh Wnt BMP Hh, Wg, Dpp: essential morphogens in wing disc * Key questions for morphogen gradient formation (1) how do they secreted (2) how do they move (3) how do they establish their activity gradients * Models for morphogen Movement Two main models Diffusion Transcytosis Other models Cytonemes Argosomes * Dpp is a morphogen in wing patterning Dpp Sal Omb P-MAD UAS-GFP-Dpp Dpp-Gal4 * Models on Dpp