Phosphorylated β-catenin localizes to centrosomes of neuronal progenitors and is required for cell polarity and neurogenesis in developing midbrain
Phosphorylated β-catenin localizes to centrosomes of neuronal progenitors and is required for cell polarity and neurogenesis in developing midbrain
复制标题
DOI：
10.1016/j.ydbio.2011.06.029
复制
发表时间：
2011-09-01
影响因子：
2.7
通讯作者：
Partanen, Juha
中科院分区：
文献类型：
--
作者：
Chilov, Dmitri;Sinjushina, Natalia;Partanen, Juha
β-连环蛋白作为 Wnt 信号通路的一部分，在细胞生长和分化以及调节细胞与 E-钙粘蛋白的粘附方面具有明确的功能。在这里，我们通过暂时控制β-连环蛋白的缺失来研究其在中脑发育中的重要性，从而可以同时分析祖细胞中完全（β-cat-null）和部分（beta-cat-low）功能丧失表型。 β-cat-null细胞不包含中心体或微管网络，并且未极化，形成分层凸起。 beta-cat-low 细胞在极性或粘附没有改变的情况下表现出有丝分裂纺锤体方向缺陷、不对称细胞分裂增加和过早分化。纺锤体缺陷与中心体 S33/S34/1-41 磷酸化 β-catenin (p-beta-cat) 减少以及中心体和微管缺陷相关。有趣的是，仅表达不可磷酸化β-连环蛋白的小鼠中的神经祖细胞与具有微管和极性缺陷的β-连环蛋白功能丧失小鼠具有多种表型。结果证明 p-β-cat 在维持神经上皮完整性方面具有新功能，并表明中心体 p-β-cat 是维持神经祖细胞对称分裂和极性所必需的。 (C) 2011 Elsevier Inc. 保留所有权利。
beta-catenin has well-established functions in cell growth and differentiation as part of the Wnt signaling pathway and in regulation of cellular adhesion with E-cadherin. Here we studied its significance in midbrain development by temporally controlled deletion of beta-catenin allowing simultaneous analysis of complete (beta-cat-null) and partial (beta-cat-low) loss-of-function phenotypes in progenitor cells. beta-cat-null cells did not contain centrosomes or a microtubule network and were unpolarized forming delaminated bulges. beta-cat-low cells displayed defects in the orientation of the mitotic spindle, increased asymmetric cell divisions and premature differentiation in absence of alterations in polarity or adhesion. The spindle defect was associated with decreased centrosomal S33/S34/1-41 phosphorylated beta-catenin (p-beta-cat) and centrosomal and microtubule defects. Interestingly, neural progenitor cells in mice expressing only unphosphorylatable beta-catenin share several phenotypes with beta-catenin loss-of-function mice with defects in microtubules and polarity. The results demonstrate a novel function for p-beta-cat in maintaining neuroepithelial integrity and suggest that centrosomal p-beta-cat is required to maintain symmetric cleavages and polarity in neural progenitors. (C) 2011 Elsevier Inc. All rights reserved.