RT Journal Article
SR Electronic
T1 MicroRNA-mediated control of developmental lymphangiogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 555664
DO 10.1101/555664
A1 Jung, Hyun Min
A1 Hu, Ciara
A1 Fister, Alexandra M.
A1 Davis, Andrew E.
A1 Castranova, Daniel
A1 Pham, Van N.
A1 Price, Lisa M.
A1 Weinstein, Brant M.
YR 2019
UL http://biorxiv.org/content/early/2019/02/20/555664.abstract
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.