Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial Cells
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 t...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-06-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/8/6/549 |
| _version_ | 1797728496643997696 |
|---|---|
| author | Xiuju Wu Jiayi Yao Lumin Wang Daoqin Zhang Li Zhang Eric X. Reynolds Tongtong Yu Kristina I. Boström Yucheng Yao |
| author_facet | Xiuju Wu Jiayi Yao Lumin Wang Daoqin Zhang Li Zhang Eric X. Reynolds Tongtong Yu Kristina I. Boström Yucheng Yao |
| author_sort | Xiuju Wu |
| collection | DOAJ |
| description | 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 (<i>Sox2</i>) 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. |
| first_indexed | 2024-03-12T11:14:52Z |
| format | Article |
| id | doaj.art-871a022756a546e4883093667e8b008c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T11:14:52Z |
| publishDate | 2019-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-871a022756a546e4883093667e8b008c2023-09-02T02:14:19ZengMDPI AGCells2073-44092019-06-018654910.3390/cells8060549cells8060549Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial CellsXiuju Wu0Jiayi Yao1Lumin Wang2Daoqin Zhang3Li Zhang4Eric X. Reynolds5Tongtong Yu6Kristina I. Boström7Yucheng Yao8Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USADivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USADivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USADivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USADivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USADivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USADivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USADivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USADivision of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, USABone 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 (<i>Sox2</i>) 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.https://www.mdpi.com/2073-4409/8/6/549Sox2bone morphogenetic proteinNotchendothelial cells |
| spellingShingle | Xiuju Wu Jiayi Yao Lumin Wang Daoqin Zhang Li Zhang Eric X. Reynolds Tongtong Yu Kristina I. Boström Yucheng Yao Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial Cells Cells Sox2 bone morphogenetic protein Notch endothelial cells |
| title | Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial Cells |
| title_full | Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial Cells |
| title_fullStr | Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial Cells |
| title_full_unstemmed | Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial Cells |
| title_short | Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial Cells |
| title_sort | crosstalk between bmp and notch induces sox2 in cerebral endothelial cells |
| topic | Sox2 bone morphogenetic protein Notch endothelial cells |
| url | https://www.mdpi.com/2073-4409/8/6/549 |
| work_keys_str_mv | AT xiujuwu crosstalkbetweenbmpandnotchinducessox2incerebralendothelialcells AT jiayiyao crosstalkbetweenbmpandnotchinducessox2incerebralendothelialcells AT luminwang crosstalkbetweenbmpandnotchinducessox2incerebralendothelialcells AT daoqinzhang crosstalkbetweenbmpandnotchinducessox2incerebralendothelialcells AT lizhang crosstalkbetweenbmpandnotchinducessox2incerebralendothelialcells AT ericxreynolds crosstalkbetweenbmpandnotchinducessox2incerebralendothelialcells AT tongtongyu crosstalkbetweenbmpandnotchinducessox2incerebralendothelialcells AT kristinaibostrom crosstalkbetweenbmpandnotchinducessox2incerebralendothelialcells AT yuchengyao crosstalkbetweenbmpandnotchinducessox2incerebralendothelialcells |