Daam2 is required for dorsal patterning via modulation of canonical Wnt signaling in the developing spinal cord.
Daam2 is required for dorsal patterning via modulation of canonical Wnt signaling in the developing spinal cord.
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DOI：
10.1016/j.devcel.2011.10.025
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发表时间：
2012-01-17
影响因子：
11.8
通讯作者：
Deneen, Benjamin
中科院分区：
文献类型：
--
作者：
Lee, Hyun Kyoung;Deneen, Benjamin
Daam家族由Daam 1和Daam 2组成。虽然Daam 1在原肠胚形成期间参与非经典Wnt信号传导，但Daam 2功能仍然完全未知。在这里，我们描述的作用Daam 2在经典的Wnt信号转导在脊髓发育。功能丧失研究表明，Daam 2是背侧祖细胞身份和经典Wnt信号传导所必需的。这些表型被β-连环蛋白拯救，表明Daam 2通过经典Wnt途径在背图案中起作用。互补的功能获得性研究表明，Daam 2通过增强配体活化来放大Wnt信号传导。生化检测发现Daam 2与Dvl 3的结合是Wnt活性和背纹形成所必需的。此外，Daam 2稳定Dvl 3/Axin 2结合，导致Dvl 3/Axin 2复合物的细胞内组装增强。这些研究表明，Daam 2调节Wnt受体复合物的形成，揭示了Daam蛋白的功能多样性以及经典Wnt信号传导如何有助于发育中脊髓的模式形成的新见解。
The Daam family of proteins consists of Daam1 and Daam2. While Daam1 participates in non-canonical Wnt signaling during gastrulation, Daam2 function remains completely uncharacterized. Here we describe the role of Daam2 in canonical Wnt signal transduction during spinal cord development. Loss-of-function studies revealed that Daam2 is required for dorsal progenitor identities and canonical Wnt signaling. These phenotypes are rescued by β-catenin, demonstrating that Daam2 functions in dorsal patterning through the canonical Wnt pathway. Complementary gain-of-function studies demonstrate that Daam2 amplifies Wnt signaling by potentiating ligand activation. Biochemical examination found that Daam2 association with Dvl3 is required for Wnt activity and dorsal patterning. Moreover, Daam2 stabilizes Dvl3/Axin2 binding, resulting in enhanced intracellular assembly of Dvl3/Axin2 complexes. These studies demonstrate that Daam2 modulates the formation of Wnt receptor complexes, revealing new insight into the functional diversity of Daam proteins and how canonical Wnt signaling contributes to pattern formation in the developing spinal cord.
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