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.
Cells. 2019 Jun 6;8(6):549. doi: 10.3390/cells8060549.
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 () 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.
骨形态发生蛋白 (BMP) 和 Notch 信号通路对于血管发育过程中的内皮细胞 (EC) 分化至关重要。最近的研究表明，BMP 活性过强会导致脑 ECs 中的 Notch 信号通路被激活，从而导致动静脉畸形 (AVMs)。然而，BMP 和 Notch 信号通路之间的串扰如何在基因调控水平上影响脑 EC 分化尚不清楚。在这里，我们报告称，BMP6 激活了激活素受体样激酶 (ALK)3，即 BMP 型 1 受体，从而诱导 Notch1 受体和 Jagged1 和 Jagged2 配体的表达。我们发现 Notch 成分的表达增加改变了 SRY-Box 2 ()启动子区域的转录调控复合物，从而诱导其在脑 ECs 中的表达。总之，我们的研究结果确定 Sox2 是 BMP 和 Notch 信号的直接靶点，并提供了关于改变的 BMP 和 Notch 信号如何影响内皮细胞转录谱的信息。
