MicroRNA-mediated control of developmental lymphangiogenesis

Abstract

The post-transcriptional mechanisms contributing to molecular regulation of developmental lymphangiogenesis and lymphatic network assembly are not well understood. Here, we use high throughput small RNA sequencing to identify miR-204, a highly conserved miRNA dramatically enriched in lymphatic vs. blood endothelial cells, and we demonstrate that this miRNA plays a critical role during lymphatic development. Suppressing miR-204 leads to loss of lymphatic vessel formation, while overproducing miR-204 in lymphatic vessels accelerates lymphatic vessel formation, suggesting a positive role during developmental lymphangiogenesis. We also identify the NFATC1 transcription factor as a key conserved target for post-transcriptional regulation by miR-204 during lymphangiogenesis. While miR-204 suppression leads to loss of lymphatics, knocking down its target NFATC1 leads to lymphatic hyperplasia, and the loss of lymphatics in miR-204-deficient animals can be rescued by NFATC1 knockdown. Together, our results highlight a miR-204/NFATC1 molecular regulatory axis required for proper lymphatic development.

Microdeletion of 16q24.1–q24.2—A unique etiology of Lymphedema–Distichiasis syndrome and neurodevelopmental disorder

“…Knock down of endothelial miRNAs have shown to result in defective lymphatic vessels development(Jung et al, 2019). Regulation of gene expression through 3 0 -UTR was shown to be directly mediated by overexpression of miR-204 and miR-495, and affected by miR-374c-5p and MiR-204-5p(Yang et al, 2017).The role of the FOXC2 3 0 -UTR deletion is further supported by the results of the current study.…”