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Open AccessArticle

Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial Cells

Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USA
Department of cell Biology and Genetics, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, China
Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang 110004, China
The Molecular Biology Institute at UCLA, Los Angeles, CA 90095-1570, USA
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(6), 549;
Received: 23 April 2019 / Revised: 31 May 2019 / Accepted: 5 June 2019 / Published: 6 June 2019
Bone morphogenetic protein (BMP) and Notch signaling are critical for endothelial cell (EC) differentiation in vascular development. Recent studies have shown that excess BMP activity induces Notch signaling in cerebral ECs resulting in arteriovenous malformation (AVMs). However, it is unclear how the crosstalk between BMP and Notch signaling affects cerebral EC differentiation at the gene regulatory level. Here, we report that BMP6 activates the activin receptor-like kinase (ALK) 3, a BMP type 1 receptor, to induce Notch1 receptor and Jagged1 and Jagged2 ligands. We show that increased expression of the Notch components alters the transcriptional regulatory complex in the SRY-Box 2 (Sox2) promoter region so as to induce its expression in cerebral ECs. Together, our results identify Sox2 as a direct target of BMP and Notch signaling and provide information on how altered BMP and Notch signaling affects the endothelial transcriptional landscape. View Full-Text
Keywords: Sox2; bone morphogenetic protein; Notch; endothelial cells Sox2; bone morphogenetic protein; Notch; endothelial cells
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Wu, X.; Yao, J.; Wang, L.; Zhang, D.; Zhang, L.; Reynolds, E.X.; Yu, T.; Boström, K.I.; Yao, Y. Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial Cells. Cells 2019, 8, 549.

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