期刊
DEVELOPMENT
卷 138, 期 7, 页码 1409-1419出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.060046
关键词
Slit/Robo; Vegf; MicroRNA; Heart tube formation; Zebrafish
资金
- Canadian Institute of Health Research
- Heart and Stroke Foundation of Canada
- National Institutes of Health [NIH T32HL007731, HL54737]
- NHLBI [P01-HL089707-01A1]
- Lawrence J. and Florence A. DeGeorge Charitable Trust/American Heart Association
- Packard Foundation
- NHLBI/NIH
- California Institute of Regenerative Medicine
- Younger Family Foundation
Members of the Slit family of secreted ligands interact with Roundabout ( Robo) receptors to provide guidance cues for many cell types. For example, Slit/Robo signaling elicits repulsion of axons during neural development, whereas in endothelial cells this pathway inhibits or promotes angiogenesis depending on the cellular context. Here, we show that miR-218 is intronically encoded in slit2 and slit3 and that it suppresses Robo1 and Robo2 expression. Our data indicate that miR-218 and multiple Slit/Robo signaling components are required for heart tube formation in zebrafish and that this network modulates the previously unappreciated function of Vegf signaling in this process. These findings suggest a new paradigm for microRNA-based control of ligand-receptor interactions and provide evidence for a novel signaling pathway regulating vertebrate heart tube assembly.
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