E-Cadherin Regulates Neural Stem Cell Self-Renewal
E-Cadherin Regulates Neural Stem Cell Self-Renewal
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DOI：
10.1523/jneurosci.0037-09.2009
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发表时间：
2009-03-25
影响因子：
5.3
通讯作者：
van der Kooy, Derek
中科院分区：
文献类型：
--
作者：
Karpowicz, Phillip;Willaime-Morawek, Sandrine;van der Kooy, Derek
E-钙粘蛋白（E-Cadherin）是一种细胞粘附蛋白，参与细胞的区室化、增殖、存活和分化。E-钙粘蛋白在体内表达于成人和胚胎前脑生发区，以及在来自这些区域并在体外生长的细胞克隆集落中表达。携带E-Cadherin floxed基因的小鼠与在Nestin启动子下表达Cre的小鼠杂交，在体内和体外都表现出神经干细胞自我更新的缺陷。E-钙粘蛋白的功能作用进一步证明使用粘附阻断抗体在体外，其特异性靶向钙粘蛋白细胞外粘附结构域。与P-钙粘蛋白抗体相反，E-钙粘蛋白抗体以剂量依赖性方式存在时，成体神经干细胞集落减少。在正常E-钙黏着蛋白和突变的E-钙黏着蛋白（不含细胞内结合结构域）过表达时，观察到克隆成体神经干细胞集落的数量增加。这些数据表明，这是特别的E-钙粘蛋白粘附，是负责这些自我更新的影响。这些数据显示了E-Cadherin在神经干细胞龛中的重要性，并表明E-Cadherin调节这些细胞的数量。
E-Cadherin, a cell adhesion protein, has been shown to take part in the compartmentalization, proliferation, survival, and differentiation of cells. E-Cadherin is expressed in the adult and embryonic forebrain germinal zones in vivo, and in clonal colonies of cells derived from these regions and grown in vitro. Mice carrying E-Cadherin floxed genes crossed to mice expressing Cre under the Nestin promoter demonstrate defects in the self-renewal of neural stem cells both in vivo and in vitro. The functional role of E-Cadherin is further demonstrated using adhesion-blocking antibodies in vitro, which specifically target cadherin extracellular adhesive domains. Adult neural stem cell colonies decrease in the presence of E-Cadherin antibodies in a dosage-dependent manner, in contrast to P-Cadherin antibody. On overexpression of normal E-Cadherin and a mutated E-Cadherin, containing no intracellular binding domain, an increased number of clonal adult neural stem cell colonies are observed. These data suggest it is specifically E-Cadherin adhesion that is responsible for these self-renewal effects. These data show the importance of E-Cadherin in the neural stem cell niche and suggest E-Cadherin regulates the number of these cells.