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EphB4 forward signalling regulates lymphatic valve development

Author

Listed:
  • 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.)

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.

Suggested Citation

  • Gu Zhang & John Brady & Wei-Ching Liang & Yan Wu & Mark Henkemeyer & Minhong Yan, 2015. "EphB4 forward signalling regulates lymphatic valve development," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7625
    DOI: 10.1038/ncomms7625
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    Cited by:

    1. Shilpa Bhatia & Diemmy Nguyen & Laurel B. Darragh & Benjamin Van Court & Jaspreet Sharma & Michael W. Knitz & Miles Piper & Sanjana Bukkapatnam & Jacob Gadwa & Thomas E. Bickett & Shiv Bhuvane & Sophi, 2022. "EphB4 and ephrinB2 act in opposition in the head and neck tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

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