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| Status |
Public on Aug 12, 2008 |
| Title |
Regulation of zebrafish endothelial gene expression by miR-126 |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by array
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| Summary |
Fish, JE, Santoro, MM, Morton, SU, Yu, S, Yeh, RF, Wythe, JD, Ivey, KI, Bruneau, BG, Stainier, DYR, and Srivastava, D. (2008). miR-126 Regulates Angiogenic Signaling and Vascular Integrity. Developmental Cell 15, 272-284.
Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-β). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function.
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| Overall design |
To identify the genes regulated by miR-126 in vivo, flk1:GFP transgenic zebrafish embryos (which express GFP in the endothelium) were injected at the one-cell stage with 4 ng of two independent antisense morpholinos that block the processing of the miR-126 pri-cursor. At 48 hours post-fertilization, endothelial cells were isolated by fluorescence-activated cell sorting from flk1:GFP transgenic fish, and RNA was extracted. Arrays were performed on four biological replicates of control and two independent miR-126 morpholinos.
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| Contributor(s) |
Fish JE, Yeh R, Srivastava D |
| Citation(s) |
18694566 |
| Submission date |
Jul 04, 2008 |
| Last update date |
Jan 25, 2018 |
| Contact name |
Jason E. Fish |
| E-mail(s) |
jefish@gladstone.ucsf.edu
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| Organization name |
J. David Gladstone Institute
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| Department |
Gladstone Institute of Cardiovascular Disease
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| Lab |
Deepak Srivastava
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| Street address |
1650 Owens Street
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL1319 |
[Zebrafish] Affymetrix Zebrafish Genome Array |
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| Samples (12)
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| GSM303576 |
zebrafish_48hpf_control_replicate1 |
| GSM303577 |
zebrafish_48hpf_miR-126 MO-1_replicate1 |
| GSM303578 |
zebrafish_48hpf_miR-126 MO-2_replicate1 |
| GSM303579 |
zebrafish_48hpf_control_replicate2 |
| GSM303580 |
zebrafish_48hpf_miR-126 MO-1_replicate2 |
| GSM303581 |
zebrafish_48hpf_miR-126 MO-2_replicate2 |
| GSM303582 |
zebrafish_48hpf_control_replicate3 |
| GSM303583 |
zebrafish_48hpf_miR-126 MO-1_replicate3 |
| GSM303584 |
zebrafish_48hpf_miR-126 MO-2_replicate3 |
| GSM303585 |
zebrafish_48hpf_control_replicate4 |
| GSM303586 |
zebrafish_48hpf_miR-126 MO-1_replicate4 |
| GSM303587 |
zebrafish_48hpf_miR-126 MO-2_replicate4 |
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| This SubSeries is part of SuperSeries: |
| GSE12039 |
Regulation of endothelial gene expression by miR-126 in human and zebrafish |
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| Relations |
| BioProject |
PRJNA114303 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12012_RAW.tar |
26.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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