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.
Date: 2019
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
MeSH Terms:
  • Animals
  • Endothelial Cells/physiology
  • Gene Expression Regulation, Developmental*
  • Humans
  • Lymphangiogenesis*
  • MicroRNAs/metabolism*
  • NFATC Transcription Factors/metabolism*
  • Zebrafish
PubMed: 31478836 Full text @ Elife
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.