Dorsal-ventral pattern of Delta trafficking is established by a snail-Tom-neuralized pathway

Dorsal-ventral pattern of Delta trafficking is established by a snail-Tom-neuralized pathway
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DOI:
10.1016/j.devcel.2006.01.011
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发表时间:
2006-02-01
期刊:
影响因子:
11.8
通讯作者:
Wieschaus, E
Wieschaus, E
中科院分区:
生物学1区
文献类型:
--
作者:
De Renzis, S;Yu, J;Wieschaus, E

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Notch配体Delta的细胞内运输在Notch途径的激活中起重要作用。我们已经解决了蜗牛依赖的调节过程中的果蝇胚胎中胚层质膜生长的三角洲贩运。我们发现,三角洲保留在中胚层的内吞囊泡,但在相邻的外胚层的表面上表达。这种贩运模式需要神经化。我们开发了一种基于染色体缺失和微阵列分析的方案,该方案导致将tom鉴定为蜗牛调节Delta运输的靶点。Snail抑制中胚层中的Tom表达,从而激活Delta运输。过表达的汤姆废除三角洲运输和信号传导到相邻的中外胚层。汤姆的损失产生中胚层型三角洲贩运在整个胚盘上皮和中外胚层基因表达的扩展。我们认为Tom拮抗Neuralized的活性,从而建立了Notch信号传导的中胚层-中外胚层边界。
The intracellular trafficking of the Notch ligand Delta plays an important role in the activation of the Notch pathway. We have addressed the snail-dependent regulation of Delta trafficking during the plasma membrane growth of the mesoderm in the Drosophila embryo. We show that Delta is retained in endocytic vesicles in the mesoderm but expressed on the surface of the adjacent ectoderm. This trafficking pattern requires Neuralized. We developed a protocol based on chromosomal deletion and microarray analysis that led to the identification of tom as the target of snail regulating Delta trafficking. Snail represses Tom expression in the mesoderm and thereby activates Delta trafficking. Overexpression of Tom abolishes Delta trafficking and signaling to the adjacent mesoectoderm. Loss of Tom produces mesoderm-type Delta trafficking in the entire blastoderm epithelium and an expansion of mesoectoderm gene expression. We propose that Tom antagonizes the activity of Neuralized and thus establishes a sharp mesoderm-mesoectoderm boundary of Notch signaling.