Identification of Novel Vascular Genes Downstream of Islet2 and Nr2f1b Transcription Factors.

The genetic regulation of vascular development is not elucidated completely. We previously characterized the transcription factors Islet2 (Isl2) and Nr2f1b as being critical for vascular growth. In this study, we further performed combinatorial microarrays to identify genes that are potentially regulated by these factors. We verified the changed expression of several targets in morphants. Those genes expressed in vessels during embryogenesis suggested their functions in vascular development. We selectively assayed a potential target ). Follistatin is known to inhibit BMP, and BMP signaling has been shown to be important for angiogenesis. However, the 's role in vascular development has not been well studied. Here, we showed the vascular defects in ISV growth and CVP patterning while overexpressing in the embryo, which mimics the phenotype of morphants. The vascular abnormalities are likely caused by defects in migration and proliferation. We further observed the altered expression of vessel markers consistent with the vascular defects in embryos. We showed that the knockdown of can rescue the vascular defects in fish, suggesting the functional specificity of . Moreover, the decreased expression of rescues abnormal vessel growth in and morphants, indicating that functions downstream of /. Lastly, we showed that Isl2/Nr2f1b control vascular development, via Fsta-BMP signaling in part. Collectively, our microarray data identify many interesting genes regulated by , which likely function in the vasculature. Our research provides useful information on the genetic control of vascular development.