Molecular pathways regulating pro-migratory effects of Hedgehog signaling
Molecular pathways regulating pro-migratory effects of Hedgehog signaling
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DOI：
10.1074/jbc.m605905200
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发表时间：
2006-11-10
影响因子：
4.8
通讯作者：
Izraeli, Shai
中科院分区：
文献类型：
--
作者：
Hochman, Eldar;Castiel, Asher;Izraeli, Shai
Hedgehog蛋白在后生动物胚胎发育中起着至关重要的作用。该通路的组成性激活与多种类型的癌症相关。最近的实验数据表明Hedgehog信号传导参与血管重塑、生殖细胞迁移和轴突引导。这些影响的分子机制仍然难以捉摸。在这里，我们表明，卵黄囊衍生的内皮细胞和胚胎成纤维细胞可以直接响应刺猬信号增加迁移在体外划痕（伤口）测定。我们还确定了这些细胞中的Hedgehog转录靶基因，其中许多参与细胞迁移，轴突导向和血管生成过程。抑制一个这样的分子通路，神经纤毛蛋白-黄单加氧酶，阻断刺猬诱导的细胞迁移。这些研究结果表明，刺猬信号直接影响胚胎内皮细胞和成纤维细胞迁移的分子和途径，已知调节细胞迁移，以响应各种环境的线索。
The Hedgehog proteins play a crucial role in metazoan embryo development. Constitutive activation of the pathway is associated with multiple types of cancer. Recent experimental data suggest involvement of Hedgehog signaling in vascular remodeling, germ cell migration, and axon guidance. The molecular mechanisms underlying these effects remain elusive. Here we show that yolk sac-derived endothelial cells and embryonic fibroblasts can directly respond to the Hedgehog signal by increased migration in an in vitro scratch (wound) assay. We also identify Hedgehog transcriptional target genes in these cells, many of which participate in cell migration, axon guidance, and angiogenesis processes. Inhibition of one such molecular pathway, neuropilin-flavomonooxygenase, blocks Hedgehog-induced cell migration. These findings suggest that Hedgehog signaling directly affects embryonic endothelial and fibroblast cell migration via molecules and pathways known to regulate cell migration in response to a variety of environmental cues.