title: EphrinB2 controls vessel pruning through STAT1-JNK3 signalling.
abstract: Angiogenesis produces primitive vascular networks that need pruning to yield hierarchically organized and functional vessels. Despite the critical importance of vessel pruning to vessel patterning and function, the mechanisms regulating this process are not clear. Here we show that EphrinB2, a well-known player in angiogenesis, is an essential regulator of endothelial cell death and vessel pruning. This regulation depends upon phosphotyrosine-EphrinB2 signalling repressing c-jun N-terminal kinase 3 activity via STAT1. JNK3 activation causes endothelial cell death. In the absence of JNK3, hyaloid vessel physiological pruning is impaired, associated with abnormal persistence of hyaloid vessels, defective retinal vasculature and microphthalmia. This syndrome closely resembles human persistent hyperplastic primary vitreus (PHPV), attributed to failed involution of hyaloid vessels. Our results provide evidence that EphrinB2/STAT1/JNK3 signalling is essential for vessel pruning, and that defects in this pathway may contribute to PHPV.
authors: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda Maryland 20892, USA.
authors: Ombretta
authors: O
authors: Salvucci
authors: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda Maryland 20892, USA.
authors: Hidetaka
authors: H
authors: Ohnuki
authors: National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Dragan
authors: D
authors: Maric
authors: National Eye Institute, National Institutes of Health, Rockville, Maryland 20852, USA.
authors: Xu
authors: X
authors: Hou
authors: National Eye Institute, National Institutes of Health, Rockville, Maryland 20852, USA.
authors: Xuri
authors: X
authors: Li
authors: Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus 43210, USA.
authors: Sung Ok
authors: SO
authors: Yoon
authors: Institute of Cell Biology and Neuroscience and BMLS, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany.
authors: Marta
authors: M
authors: Segarra
authors: Department of Pathology, Ophthalmology and Oncology, Johns Hopkins University, Baltimore, Maryland 21287, USA.
authors: Charles G
authors: CG
authors: Eberhart
authors: 1] Institute of Cell Biology and Neuroscience and BMLS, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany [2] Focus Program Translational Neuroscience, Johannes Gutenberg University Mainz, Mainz, Germany.
authors: Amparo
authors: A
authors: Acker-Palmer
authors: Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda Maryland 20892, USA.
authors: Giovanna
authors: G
authors: Tosato
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D047369:Chromatin Immunoprecipitation; D042783:Endothelial Cells / Q000378:metabolism*; D036388:Ephrin-B2 / Q000235:genetics*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics*; D054514:Persistent Hyperplastic Primary Vitreous / Q000235:genetics; D012171:Retinal Vessels / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D036388:Ephrin-B2; D050794:STAT1 Transcription Factor; D048057:Mitogen-Activated Protein Kinase 10