|ZFIN ID: ZDB-PUB-190904-2|
MicroRNA-mediated control of developmental lymphangiogenesis
Jung, H.M., Hu, C.T., Fister, A.M., Davis, A.E., Castranova, D., Pham, V.N., Price, L.M., Weinstein, B.M.
|Source:||eLIFE 8: (Journal)|
|Registered Authors:||Castranova, Dan, Davis, Andrew, Fister, Alexandra, Jung, Hyun Min, Pham, Van, Weinstein, Brant M.|
|Keywords:||developmental biology, embryo, lymphangiogenesis, lymphatic development, lymphatic vessel, miR-204, nfatc1, zebrafish|
|PubMed:||31478836 Full text @ Elife|
Jung, H.M., Hu, C.T., Fister, A.M., Davis, A.E., Castranova, D., Pham, V.N., Price, L.M., Weinstein, B.M. (2019) MicroRNA-mediated control of developmental lymphangiogenesis. eLIFE. 8:.
ABSTRACTThe 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.