Identification of Potential Modulators of BMP signaling during Venous Angiogenesis in Zebrafish

Abstract

Bone morphogenetic protein (BMP) signaling selectively induces angiogenesis from veins during the development. Although the gradient of BMP signaling is critical role for this process, it is not clear how the ligand gradient is determined. For other tissues and organs that are regulated by BMP signaling, the gradient of BMP signaling is regulated by various BMP antagonists. Therefore, it is likely that angiogenesis in response to BMP stimulation is similarly regulated by the BMP antagonists. To identify BMP antagonists which are essential for BMP gradient formation during angiogenesis, combined screen using in situ hybridization and qRT-PCR was performed. While many BMP antagonists highly expressed, gremlin2b, follistatin like 1a and 1b were continuously expressed during development. Moreover, in situ hybridization-based expression analysis showed gremlin2b, follistatin like 1a and 1b highly expressed in the caudal vein plexus region of the zebrafish, hinting their activities contribute to formation of the caudal vein plexus.