EphrinB2-EphB4-RASA1 Signaling in Human Cerebrovascular Development and Disease.

1. Trends Mol Med. 2019 Apr;25(4):265-286. doi: 10.1016/j.molmed.2019.01.009. Epub 2019 Feb 25. EphrinB2-EphB4-RASA1 Signaling in Human Cerebrovascular Development and Disease. Zeng X(1), Hunt A(2), Jin SC(3), Duran D(2), Gaillard J(2), Kahle KT(4). Author information: (1)Department of Genetics, Yale School of Medicine, New Haven CT, USA; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA. (2)Department of Neurosurgery, Yale School of Medicine, New Haven CT, USA. (3)Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA. (4)Department of Neurosurgery, Yale School of Medicine, New Haven CT, USA; Department of Pediatrics, Yale School of Medicine, New Haven CT, USA; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven CT, USA. Electronic address: kristopher.kahle@yale.edu. Recent whole exome sequencing studies in humans have provided novel insight into the importance of the ephrinB2-EphB4-RASA1 signaling axis in cerebrovascular development, corroborating and extending previous work in model systems. Here, we aim to review the human cerebrovascular phenotypes associated with ephrinB2-EphB4-RASA1 mutations, including those recently discovered in Vein of Galen malformation: the most common and severe brain arteriovenous malformation in neonates. We will also discuss emerging paradigms of the molecular and cellular pathophysiology of disease-causing ephrinB2-EphB4-RASA1 mutations, including the potential role of somatic mosaicism. These observations have potential diagnostic and therapeutic implications for patients with rare congenital cerebrovascular diseases and their families. Copyright © 2019 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.molmed.2019.01.009 PMCID: PMC6456402 PMID: 30819650 [Indexed for MEDLINE]