| Summary: | 碩士 === 國立臺灣大學 === 生命科學系 === 103 === Vessel formation, including angiogenesis and lymphangiogenesis, paves the structural foundation of circulation. The study of vessel formation in vertebrates often hinders by the invisibility, but the availability of transparent zebrafish embryos greatly accelerates our understanding in the field. With the addition of several vessel reporter lines, zebrafish has become one of the popular models to explore the regulatory mechanisms of angiogenesis and lymphangiogenesis. microRNAs (miRNAs) have been reported to be involved in regulating angiogenesis and lymphangiogenesis. In particularly, several miRNAs have been shown to be enriched in blood endothelial cells. However, except miR-221, the functional roles of other miRNAs remain unknown. Here, I first validated the enrichment of those miRNAs in endothelial cells from embryos at 22-48 h post fertilization. Interestingly, I found one of miRNAs, miR-19c, increases notably during 22-48 hpf. This time is associated with blood vessel and lymphatic vessel formation, I hypothesized that miR-19c may regulate blood or lymphatic vessel formation.
I performed loss and gain of function analyses by applying antisense morpholino/miRNA inhibitor and miRNA mimic against miR-19c to different transgenic zebrafish lines expressing GFP. I observed that overexpression of miR-19c impaired lymphatic development, but no significant change in blood vascular system was observed in embryos. Transforming growth factor beta1a (tgfβ1a) is a potential target of miR-19c and known lymphangiogenesis regulator. I found significant reduction of the expression of tgfβ1a in embryos injected with miR-19c mimic. The functional link between miR-19c and tgfβ1a still needs to be investigated. Collectively, I conclude that miR-19c is indispensable to lymphatic development in zebrafish possibly via tgfβ1a.
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