MicroRNA-mediated control of developmental lymphangiogenesis

eLife

Hyun Min Jung¹  Lisa M Price¹  Van N Pham¹  Andrew E Davis¹  Alexandra M Fister¹  Daniel Castranova¹  Brant M Weinstein¹  Ciara T Hu¹ 

[1] Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United States;

关键词: miR-204;    nfatc1;    lymphangiogenesis;    lymphatic vessel;    lymphatic development;    embryo;   

DOI  :  10.7554/eLife.46007

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown