MicroRNA-mediated control of developmental lymphangiogenesis
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 identif...
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doaj-c87d39380fb64abf8f91b343e8c89c722021-05-05T17:53:24ZengeLife Sciences Publications LtdeLife2050-084X2019-09-01810.7554/eLife.46007MicroRNA-mediated control of developmental lymphangiogenesisHyun Min Jung0https://orcid.org/0000-0001-8892-0941Ciara T Hu1Alexandra M Fister2Andrew E Davis3Daniel Castranova4Van N Pham5Lisa M Price6Brant M Weinstein7https://orcid.org/0000-0003-4136-4962Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesThe 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.https://elifesciences.org/articles/46007miR-204nfatc1lymphangiogenesislymphatic vessellymphatic developmentembryo |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hyun Min Jung Ciara T Hu Alexandra M Fister Andrew E Davis Daniel Castranova Van N Pham Lisa M Price Brant M Weinstein |
spellingShingle |
Hyun Min Jung Ciara T Hu Alexandra M Fister Andrew E Davis Daniel Castranova Van N Pham Lisa M Price Brant M Weinstein MicroRNA-mediated control of developmental lymphangiogenesis eLife miR-204 nfatc1 lymphangiogenesis lymphatic vessel lymphatic development embryo |
author_facet |
Hyun Min Jung Ciara T Hu Alexandra M Fister Andrew E Davis Daniel Castranova Van N Pham Lisa M Price Brant M Weinstein |
author_sort |
Hyun Min Jung |
title |
MicroRNA-mediated control of developmental lymphangiogenesis |
title_short |
MicroRNA-mediated control of developmental lymphangiogenesis |
title_full |
MicroRNA-mediated control of developmental lymphangiogenesis |
title_fullStr |
MicroRNA-mediated control of developmental lymphangiogenesis |
title_full_unstemmed |
MicroRNA-mediated control of developmental lymphangiogenesis |
title_sort |
microrna-mediated control of developmental lymphangiogenesis |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2019-09-01 |
description |
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. |
topic |
miR-204 nfatc1 lymphangiogenesis lymphatic vessel lymphatic development embryo |
url |
https://elifesciences.org/articles/46007 |
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