Deciphering the role of BMP9-BMP10 and YAP-TEAD signaling in vascular smooth muscle heterogeneity and pulmonary hypertension (A02)

• Subject Area: Developmental Biology
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 268555672

BMP9 and BMP10 bind to the ALK1 receptor, which is linked to pulmonary hypertension (PH). We found that genetic inactivation of BMP9/10 in mice causes dramatic changes in vascular tone and diminution of vascular smooth muscle cells (VSMC), protecting mice from hypoxia-induced PH. These effects are mediated by vascular bed-specific expression of Alk receptors in VSMC. We will elucidate the impact of the BMP9/BMP10/Alk1 axis on reverse remodeling of pulmonary arteries, analyze the meaning of heterogeneous Alk-receptor expression in VSMCs, explore the cross-talk between Alk1/Smad1/5/8 and YAP-TEAD signaling and elucidate the impact of BMP9/10 dependent differential splicing in VSMCs.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1213: Pulmonary Hypertension and Cor Pulmonale
• Applicant Institution: Justus-Liebig-Universität Gießen
• Project Heads: Professor Dr. Saverio Bellusci; Professor Dr. Thomas Braun