[HTML][HTML] EphB4 forward signalling regulates lymphatic valve development

G Zhang, J Brady, WC Liang, Y Wu… - Nature …, 2015 - nature.com
G Zhang, J Brady, WC Liang, Y Wu, M Henkemeyer, M Yan
Nature communications, 2015nature.com
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 …
Abstract
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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