Follistatin‐BMP Signaling Regulated by Isl2/CoupTFIb is Critical for Vascular Development

Abstract

While many regulators and signaling molecules controlling the process of vascular development are in zebrfish, genetic regulating the vein identity, intersegmental vessels (ISV) and cardinal vein plexus (CVP) patterning is still not fully understood. We previously identified the transcription factors isl2/coupTFIb required for specification of the vein and ISV growth mediated by Notch pathway in zebrafish. Microarray analysis showed highly overlapping downstream targets controlled by isl2/coupTFIb, suggesting that cooperatively regulate vascular development. In this study, we analyze the functional relevance of one potential target from array hits, follistatin 1a (fst1a). Fst1a is a bone morphogenetic protein (BMP) antagonist related to axis formation during the development and shown involved in venous angiogenesis. However, no description of fst1a functioning in vascular so far. The interaction of notch and BMP signalings to regulate vasculization is unknown.We first examine amino acid sequence comparison and show fst1a is highly conserved among the vertebrates. Our in‐situ hybridization results showed fst1a is expressed in the lateral plate mesoderm and vessels. Overexpressing fst1a driven by fli1 promoter in zebrafish embryos, we observe the vascular defects in the growth of ISV and CVP. We further address the genetic interaction between fst1a and isl2, we found fst1 expression is increased in isl2 morphants by in‐situ hybridization. In addition, knockdown of fst1a can partial rescue the vascular defects in isl2 morphants. We suggest fst1a likely regulated by isl2. Since fst1 involved in BMP and isl2 functions downstream of notch, we conclude fst1a‐BMP signaling play an important role to regulate vascular patterning and interacts with isl2/coupTFIb‐Notch signaling.