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Publication : EphB4 forward signalling regulates lymphatic valve development.

First Author  Zhang G Year  2015
Journal  Nat Commun Volume  6
Pages  6625 PubMed ID  25865237
Mgi Jnum  J:222726 Mgi Id  MGI:5645431
Doi  10.1038/ncomms7625 Citation  Zhang G, et al. (2015) EphB4 forward signalling regulates lymphatic valve development. Nat Commun 6:6625
abstractText  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.
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