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Published on: April 23, 2021
EphrinB2-EphB4-RASA1 Signaling in Human Cerebrovascular Development and Disease
Xue Zeng1, Ava Hunt2, Sheng Chih Jin3
1Department of Genetics, Yale School of Medicine, New Haven CT, USA; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.
Abstract:
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.
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