EphB4 forward signalling regulates lymphatic valve development

Gu Zhang, John Brady, Wei Ching Liang, Yan Wu, Mark Henkemeyer, Minhong Yan

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish (US)
Article number6625
JournalNature Communications
Volume6
DOIs
StatePublished - Apr 13 2015

Fingerprint

Ephrins
antibodies
mice
mutations
cells
Blocking Antibodies
Bearings (structural)
Phosphotransferases
Mutation
Antibodies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

EphB4 forward signalling regulates lymphatic valve development. / Zhang, Gu; Brady, John; Liang, Wei Ching; Wu, Yan; Henkemeyer, Mark; Yan, Minhong.

In: Nature Communications, Vol. 6, 6625, 13.04.2015.

Research output: Contribution to journalArticle

Zhang, Gu ; Brady, John ; Liang, Wei Ching ; Wu, Yan ; Henkemeyer, Mark ; Yan, Minhong. / EphB4 forward signalling regulates lymphatic valve development. In: Nature Communications. 2015 ; Vol. 6.
@article{41dbb2bae30a408c94b8c2118f122ca6,
title = "EphB4 forward signalling regulates lymphatic valve development",
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.",
author = "Gu Zhang and John Brady and Liang, {Wei Ching} and Yan Wu and Mark Henkemeyer and Minhong Yan",
year = "2015",
month = "4",
day = "13",
doi = "10.1038/ncomms7625",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - EphB4 forward signalling regulates lymphatic valve development

AU - Zhang, Gu

AU - Brady, John

AU - Liang, Wei Ching

AU - Wu, Yan

AU - Henkemeyer, Mark

AU - Yan, Minhong

PY - 2015/4/13

Y1 - 2015/4/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84927947282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84927947282&partnerID=8YFLogxK

U2 - 10.1038/ncomms7625

DO - 10.1038/ncomms7625

M3 - Article

C2 - 25865237

AN - SCOPUS:84927947282

VL - 6

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 6625

ER -