PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature

Mäkinen, Taija; Adams, Ralf H; Bailey, John; Lu, Qiang; Ziemiecki, Andrew; Alitalo, Kari; Klein, Rüdiger; Wilkinson, George A (2005). PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature. Genes & development, 19(3), pp. 397-410. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press 10.1101/gad.330105

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The transmembrane ligand ephrinB2 and its cognate Eph receptor tyrosine kinases are important regulators of embryonic blood vascular morphogenesis. However, the molecular mechanisms required for ephrinB2 transduced cellular signaling in vivo have not been characterized. To address this question, we generated two sets of knock-in mice: ephrinB2DeltaV mice expressed ephrinB2 lacking the C-terminal PDZ interaction site, and ephrinB2(5F) mice expressed ephrinB2 in which the five conserved tyrosine residues were replaced by phenylalanine to disrupt phosphotyrosine-dependent signaling events. Our analysis revealed that the homozygous mutant mice survived the requirement of ephrinB2 in embryonic blood vascular remodeling. However, ephrinB2DeltaV/DeltaV mice exhibited major lymphatic defects, including a failure to remodel their primary lymphatic capillary plexus into a hierarchical vessel network, hyperplasia, and lack of luminal valve formation. Unexpectedly, ephrinB2(5F/5F) mice displayed only a mild lymphatic phenotype. Our studies define ephrinB2 as an essential regulator of lymphatic development and indicate that interactions with PDZ domain effectors are required to mediate its functions.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital (discontinued) > Forschungsgruppe Biologie und Karzinogenese der Brustdrüse (discontinued)

UniBE Contributor:

Ziemiecki, Andrew

ISSN:

0890-9369

Publisher:

Cold Spring Harbor Laboratory Press

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:12

Last Modified:

06 Dec 2013 13:58

Publisher DOI:

10.1101/gad.330105

PubMed ID:

15687262

Web of Science ID:

000226800100011

URI:

https://boris.unibe.ch/id/eprint/31742 (FactScience: 196409)

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