PT  - JOURNAL ARTICLE
AU  - Hyun Min Jung
AU  - Ciara Hu
AU  - Alexandra M. Fister
AU  - Andrew E. Davis
AU  - Daniel Castranova
AU  - Van N. Pham
AU  - Lisa M. Price
AU  - Brant M. Weinstein
TI  - MicroRNA-mediated control of developmental lymphangiogenesis
AID  - 10.1101/555664
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 555664
4099  - http://biorxiv.org/content/early/2019/02/20/555664.short
4100  - http://biorxiv.org/content/early/2019/02/20/555664.full
AB  - 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.