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新型研究揭示 Snail2 对神经嵴细胞迁移过程中αN-连环蛋白功能和调控的影响。

Novel insight into the function and regulation of alphaN-catenin by Snail2 during chick neural crest cell migration.

机构信息

Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA.

出版信息

Dev Biol. 2010 Aug 15;344(2):896-910. doi: 10.1016/j.ydbio.2010.06.006. Epub 2010 Jun 11.

Abstract

The neural crest is a transient population of migratory cells that differentiates to form a variety of cell types in the vertebrate embryo, including melanocytes, the craniofacial skeleton, and portions of the peripheral nervous system. These cells initially exist as adherent epithelial cells in the dorsal aspect of the neural tube and only later become migratory after an epithelial-to-mesenchymal transition (EMT). Snail2 plays a critical role in mediating chick neural crest cell EMT and migration due to its expression by both premigratory and migratory cranial neural crest cells and its ability to down-regulate intercellular junctions components. In an attempt to delineate the role of cellular junction components in the neural crest, we have identified the adherens junction molecule neural alpha-catenin (alphaN-catenin) as a Snail2 target gene whose repression is critical for chick neural crest cell migration. Knock-down and overexpression of alphaN-catenin enhances and inhibits neural crest cell migration, respectively. Furthermore, our results reveal that alphaN-catenin regulates the appropriate movement of neural crest cells away from the neural tube into the embryo. Collectively, our data point to a novel function of an adherens junction protein in facilitating the proper migration of neural crest cells during the development of the vertebrate embryo.

摘要

神经嵴是一种短暂存在的迁移细胞群体,可分化为脊椎动物胚胎中的多种细胞类型,包括黑色素细胞、颅面骨骼和部分周围神经系统。这些细胞最初作为粘附的上皮细胞存在于神经管的背侧,仅在发生上皮-间充质转化(EMT)后才成为迁移细胞。由于其在预先迁移和迁移的颅神经嵴细胞中表达,并且能够下调细胞间连接成分,Snail2 在介导鸡神经嵴细胞 EMT 和迁移中起着关键作用。为了阐明细胞连接成分在神经嵴中的作用,我们已经确定了粘附连接分子神经α-连环蛋白(αN-连环蛋白)作为 Snail2 的靶基因,其抑制对于鸡神经嵴细胞迁移至关重要。αN-连环蛋白的敲低和过表达分别增强和抑制神经嵴细胞迁移。此外,我们的结果表明,αN-连环蛋白调节神经嵴细胞从神经管向胚胎适当移动。总之,我们的数据表明,粘附连接蛋白在促进脊椎动物胚胎发育过程中神经嵴细胞的正确迁移方面具有新的功能。

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