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MicroRNA-mediated control of developmental lymphangiogenesis

Hyun Min Jung, Ciara Hu, Alexandra M. Fister, Andrew E. Davis, Daniel Castranova, Van N. Pham, Lisa M. Price, View ORCID ProfileBrant M. Weinstein
doi: https://doi.org/10.1101/555664
Hyun Min Jung
Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892
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Ciara Hu
Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892
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Alexandra M. Fister
Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892
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Andrew E. Davis
Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892
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Daniel Castranova
Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892
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Van N. Pham
Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892
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Lisa M. Price
Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892
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Brant M. Weinstein
Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892
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  • ORCID record for Brant M. Weinstein
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ABSTRACT

The post-transcriptional mechanisms contributing to molecular regulation of developmental lymphangiogenesis and lymphatic network assembly are not well understood. Here, we use high throughput small RNA sequencing to identify miR-204, a highly conserved miRNA dramatically enriched in lymphatic vs. blood endothelial cells, and we demonstrate that this miRNA plays a critical role during lymphatic development. Suppressing miR-204 leads to loss of lymphatic vessel formation, while overproducing miR-204 in lymphatic vessels accelerates lymphatic vessel formation, suggesting a positive role during developmental lymphangiogenesis. We also identify the NFATC1 transcription factor as a key conserved target for post-transcriptional regulation by miR-204 during lymphangiogenesis. While miR-204 suppression leads to loss of lymphatics, knocking down its target NFATC1 leads to lymphatic hyperplasia, and the loss of lymphatics in miR-204-deficient animals can be rescued by NFATC1 knockdown. Together, our results highlight a miR-204/NFATC1 molecular regulatory axis required for proper lymphatic development.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 20, 2019.
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MicroRNA-mediated control of developmental lymphangiogenesis
Hyun Min Jung, Ciara Hu, Alexandra M. Fister, Andrew E. Davis, Daniel Castranova, Van N. Pham, Lisa M. Price, Brant M. Weinstein
bioRxiv 555664; doi: https://doi.org/10.1101/555664
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MicroRNA-mediated control of developmental lymphangiogenesis
Hyun Min Jung, Ciara Hu, Alexandra M. Fister, Andrew E. Davis, Daniel Castranova, Van N. Pham, Lisa M. Price, Brant M. Weinstein
bioRxiv 555664; doi: https://doi.org/10.1101/555664

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