6533b7d5fe1ef96bd12646a3

RESEARCH PRODUCT

EphrinB2 controls vessel pruning through STAT1-JNK3 signalling

Dragan MaricOmbretta SalvucciGiovanna TosatoXuri LiXu HouAmparo Acker-palmerCharles G. EberhartSung Ok YoonHidetaka OhnukiMarta Segarra

subject

Chromatin ImmunoprecipitationCell SurvivalAngiogenesisImmunoblottingRegulatorFluorescent Antibody TechniqueNeovascularization PhysiologicGeneral Physics and AstronomyEphrin-B2Persistent Hyperplastic Primary VitreousIn Vitro TechniquesBiologyBioinformaticsMicrophthalmiaArticleGeneral Biochemistry Genetics and Molecular BiologyNeovascularizationMiceMitogen-Activated Protein Kinase 10Human Umbilical Vein Endothelial CellsmedicineAnimalsHumansImmunoprecipitationInvolution (medicine)Pruning (decision trees)Cell ProliferationMice KnockoutMultidisciplinaryNeovascularization PathologicfungiEndothelial CellsRetinal VesselsGeneral ChemistryFlow Cytometrymedicine.diseaseCell biologyEndothelial stem cellSTAT1 Transcription Factornervous systemPersistent hyperplastic primary vitreousGene Knockdown Techniquescardiovascular systemmedicine.symptomSignal Transduction

description

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.

yearjournalcountryeditionlanguage
2014-08-26Nature Communications
https://doi.org/10.1038/ncomms7576