EphB4 forward signalling regulates lymphatic valve development.
EphB4 forward signalling regulates lymphatic valve development.
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DOI：
10.1038/ncomms7625
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发表时间：
2015-04-13
影响因子：
16.6
通讯作者：
Yan, Minhong
中科院分区：
文献类型：
--
作者：
Zhang, Gu;Brady, John;Liang, Wei-Ching;Wu, Yan;Henkemeyer, Mark;Yan, Minhong
双向信号传递被认为是Eph-EPhin信号系统的一个显著标志：在表达Eph的细胞中依赖于Eph的正向信号，在表达EPhin的细胞中依赖于ePhin的反向信号。依从性反向信号传递的概念来自于利用携带突变的小鼠的细胞内区域进行的基因实验。在这里，我们证明了依赖于EphB4的正向信号调节淋巴瓣的发育，这个过程以前被认为是由依赖于EphB4的反向信号调节的。我们开发了选择性地针对EphB4和ephinB2的抗体。我们发现，携带EphB4依赖的前向信号的EphB4基因改变细胞质区域的小鼠已经显著改变。使用功能性封闭抗体选择性抑制EphB4会导致淋巴瓣发育缺陷。此外，化学遗传学方法被用来明确地表明EphB4的激酶活性对于淋巴瓣的发育是必不可少的。双向的Eph-Eparin信号调节着无数的发育项目。张某等人。表明EphB4正向信号对淋巴瓣膜的发育至关重要，为这一重要的发育过程提供了新的见解，以前被认为是由依赖ePhrinB2的反向信号调节的。
Bidirectional signalling is regarded as a notable hallmark of the Eph-ephrin signalling system: Eph-dependent forward signalling in Eph-expressing cells and ephrin-dependent reverse signalling in Ephrin-expressing cells. The notion of ephrin-dependent reverse signalling derives from genetic experiments utilizing mice carrying mutations in the intracellular region of ephrinBs. Here we show that EphB4-dependent forward signalling regulates lymphatic valve development, a process previously thought to be regulated by ephrinB2-dependent reverse signalling. We develop antibodies that selectively target EphB4 and ephrinB2. We find that mice bearing genetically altered cytoplasmic region of ephrinB2 have significantly altered EphB4-dependent forward signalling. Selective inhibition of EphB4 using a functional blocking antibody results in defective lymphatic valve development. Furthermore, a chemical genetic approach is used to unequivocally show that the kinase activity of EphB4 is essential for lymphatic valve development. The bidirectional Eph-ephrin signalling regulates a myriad of developmental programmes. Zhang et al. show that EphB4 forward signalling is crucial for lymphatic valve development, providing new insight into this important developmental process previously thought to be regulated by ephrinB2-dependent reverse signalling.
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影响因子：
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作者：
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作者：
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通讯作者：
Henkemeyer, M