EphB4 forward signalling regulates lymphatic valve development

Gu Zhang, John Brady, Wei-Ching Liang, Yan Wu, Mark Henkemeyer and Minhong Yan ()
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Gu Zhang: Genentech Inc.
John Brady: Genentech Inc.
Wei-Ching Liang: Genentech Inc.
Yan Wu: Genentech Inc.
Mark Henkemeyer: University of Texas Southwestern Medical Center
Minhong Yan: Genentech Inc.

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7625

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