The role of mitotic asymmetries for Wnt and Bmp signaling

有丝分裂不对称对 Wnt 和 Bmp 信号传导的作用

• 批准号: 189220577
• 负责人: Dr. Philipp Vick
• 金额: --
• 依托单位: Fachgebiet Zoologie (190z)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/189220577?language=en
• 关键词: role; mitotic; asymmetries; Wnt; Bmp

Wnt signaling is active in embryonic stem cells and important for anterior-posterior (head-tail) axis establishment during embryogenesis. Bmp signaling controls the dorso-ventral (back-belly) axis and together Wnt and Bmp create a Cartesian coordinate system in the embryo. Intercommunication has been shown at the level of the Bmp transcription factor Smad1, whose degradation is prevented by Wnt signals. Importantly, Smad1 and many other proteins tagged for degradation by phosphorylation unequally accumulate near the cell nucleus of dividing embryonic and somatic cells. Thus, one of the daughter cell inherits more of the relevant proteins, raising questions about the regulation of this mechanism and its function for cell divisions and embryonic development. In preliminary cell line experiments we found this process of asymmetric sorting significantly increased by Wnt treatment. Importantly, this caused asymmetric accumulation of activated signaling components in the nucleus of the corresponding cell as well. In this project, I will first investigate the nature of the influence of Wnt signals on cellular asymmetries. As a second part, I will analyze if these asymmetries reflect differences in signaling activity of two daughter cells by using different approaches. It would be of great importance to reveal if Wnt and Bmp signaling are asymmetric as well, implying different fates for the daughter cells. Finally, these analyses will be extended to embryos to uncover if this is a general polarity phenomenon of dividing cells and to connect the features with overall regulation of axis development by Wnt and Bmp. In sum, this project will help to explain how general binary decisions made during cell division are related to embryonic axis development in complex embryos.

Wnt信号在胚胎干细胞中是活跃的，并且对于胚胎发生期间的前后（头-尾）轴建立是重要的。BMP信号传导控制背腹（后腹）轴，Wnt和BMP一起在胚胎中创建笛卡尔坐标系。已显示在Bmp转录因子Smad 1的水平上的相互通信，其降解被Wnt信号阻止。重要的是，Smad 1和许多其他标记为通过磷酸化降解的蛋白质在分裂的胚胎和体细胞的细胞核附近不均匀地积累。因此，其中一个子细胞继承了更多的相关蛋白质，这就提出了关于这种机制的调节及其在细胞分裂和胚胎发育中的功能的问题。在初步的细胞系实验中，我们发现Wnt处理显著增加了这种不对称分选过程。重要的是，这也导致了相应细胞核中激活的信号成分的不对称积累。在这个项目中，我将首先研究Wnt信号对细胞不对称性影响的性质。作为第二部分，我将通过使用不同的方法来分析这些不对称性是否反映了两个子细胞信号活性的差异。揭示Wnt和Bmp信号是否也是不对称的，这意味着子细胞的命运不同，这将是非常重要的。最后，这些分析将扩展到胚胎，以揭示这是否是分裂细胞的一般极性现象，并将这些特征与Wnt和Bmp对轴发育的整体调节联系起来。总之，该项目将有助于解释细胞分裂过程中的一般二元决策如何与复杂胚胎中的胚胎轴发育相关。