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EphB4 forward signalling regulates lymphatic valve development

Identifieur interne : 001E30 ( Main/Exploration ); précédent : 001E29; suivant : 001E31

EphB4 forward signalling regulates lymphatic valve development

Auteurs : Gu Zhang [États-Unis] ; John Brady [États-Unis] ; Wei-Ching Liang [États-Unis] ; Yan Wu [États-Unis] ; Mark Henkemeyer [États-Unis] ; Minhong Yan [États-Unis]

Source :

RBID : PMC:4403310

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.


Url:
DOI: 10.1038/ncomms7625
PubMed: 25865237
PubMed Central: 4403310


Affiliations:


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