Context-dependent signaling defines roles of BMP9 and BMP10 in embryonic and postnatal development

Hao Chen, John Brady Ridgway, Tao Sai, Joyce Lai, Soren Warming, Hanying Chen, Merone Roose-Girma, Gu Zhang, Weinian Shou, Minhong Yan

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Many important signaling pathways rely on multiple ligands. It is unclear if this is a mechanism of safeguard via redundancy or if it serves other functional purposes. In this study, we report unique insight into this question by studying the activin receptor-like kinase 1 (ALK1) pathway. Despite its functional importance in vascular development, the physiological ligand or ligands for ALK1 remain to be determined. Using conventional knockout and specific antibodies against bone morphogenetic protein 9 (BMP9) or BMP10, we showed that BMP9 and BMP10 are the physiological, functionally equivalent ligands of ALK1 in vascular development. Timing of expression dictates the in vivo requisite role of each ligand, and concurrent expression results in redundancy. We generated mice (Bmp109/9) in which the coding sequence of Bmp9 replaces that of Bmp10. Surprisingly, analysis of Bmp109/9 mice demonstrated that BMP10 has an exclusive function in cardiac development, which cannot be substituted by BMP9. Our study reveals context-dependent significance in having multiple ligands in a signaling pathway.

Original languageEnglish (US)
Pages (from-to)11887-11892
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number29
DOIs
StatePublished - Jul 16 2013

Keywords

  • Angiogenesis
  • Heart Development
  • Heart Homeostasis
  • Hereditary Hemorrhagic Telangiectasia

ASJC Scopus subject areas

  • General

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