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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.

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.

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.

KEYWORDS:

Vein of Galen malformation; arteriovenous malformation; cerebrovascular disorders; ephrin signaling; neurosurgery; vasculogenesis

PMID:
30819650
PMCID:
PMC6456402
[Available on 2020-04-01]
DOI:
10.1016/j.molmed.2019.01.009

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