MicroRNA-mediated control of developmental lymphangiogenesis

• Main Authors: Hyun Min Jung, Ciara T Hu, Alexandra M Fister, Andrew E Davis, Daniel Castranova, Van N Pham, Lisa M Price, Brant M Weinstein
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2019-09-01
• Series: eLife
• Subjects: miR-204; nfatc1; lymphangiogenesis; lymphatic vessel; lymphatic development; embryo
• Online Access: https://elifesciences.org/articles/46007

The post-transcriptional mechanisms contributing to molecular regulation of developmental lymphangiogenesis and lymphatic network assembly are not well understood. MicroRNAs are important post-transcriptional regulators during development. Here, we use high throughput small RNA sequencing to identify miR-204, a highly conserved microRNA dramatically enriched in lymphatic vs. blood endothelial cells in human and zebrafish. Suppressing miR-204 leads to loss of lymphatic vessels while endothelial overproduction of miR-204 accelerates lymphatic vessel formation, suggesting a critical positive role for this microRNA during developmental lymphangiogenesis. We also identify the NFATC1 transcription factor as a key miR-204 target in human and zebrafish, and show that NFATC1 suppression leads to lymphatic hyperplasia. The loss of lymphatics caused by miR-204 deficiency can be largely rescued by either endothelial autonomous expression of miR-204 or by suppression of NFATC1. Together, our results highlight a miR-204/NFATC1 molecular regulatory axis required for proper lymphatic development.