miR-19c?Regulates Lymphatic Vessel Development Through Tgfβ1a

MicroRNAs (miRNA) are known regulators of gene expression in different cellular processes including development. Recently, different miRNAs were found to be enriched in endothelial cells (ECs) that suggests a role of miRNA in vascular development. miRNAs have been shown to mediate blood vessel development. However, their role in lymphatic vessel development is less well understood. Using zebrafish as a model, we analyzed miRNAs in ECs and found one miRNA, miR-19c, with increased expression between 24 to 48 hours post fertilization (hpf). We show that knocking down miR-19c by morpholino oligonucleotides has no effect on blood or lymphatic vasculature, while over expression by injecting miRNA mimic causes over-branching of lymphatic vessels. This suggests miR-19c as a positive regulator of lymphatic development. One probable target of miR-19c is transforming growth factor β 1a (tgfβ1a). Tgfβ1a may have the potential to prevent lymphangiogenesis and promote angiogenesis. Thus, we co-injected miR-19c mimic with tgfβ1a and they lessened the lymphatic defects observed. Moreover, we validated that tgfβ1a is a direct target of miR19c by Luciferase assay. Taken together, these results demonstrate that miR-19c is a positive gene regulator of lymphatic development and targets tgfβ1a to reduce anti-lymphatic signals during development.