miR-221 is required for endothelial tip cell behaviors during vascular development
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Authors
Nicoli, StefaniaKnyphausen, Carl-Philipp
Zhu, Lihua Julie
Lakshmanan, Abirami
Lawson, Nathan D.
UMass Chan Affiliations
Program in Gene Function and ExpressionDocument Type
Journal ArticlePublication Date
2012-02-14
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Angiogenesis requires coordination of distinct cell behaviors between tip and stalk cells. Although this process is governed by regulatory interactions between the vascular endothelial growth factor (Vegf) and Notch signaling pathways, little is known about the potential role of microRNAs. Through deep sequencing and functional screening in zebrafish, we find that miR-221 is essential for angiogenesis. miR-221 knockdown phenocopied defects associated with loss of the tip cell-expressed Flt4 receptor. Furthermore, miR-221 was required for tip cell proliferation and migration, as well as tip cell potential in mosaic blood vessels. miR-221 knockdown also prevented "hyper-angiogenesis" defects associated with Notch deficiency and miR-221 expression was inhibited by Notch signaling. Finally, miR-221 promoted tip cell behavior through repression of two targets: cyclin dependent kinase inhibitor 1b (cdkn1b) and phosphoinositide-3-kinase regulatory subunit 1 (pik3r1). These results identify miR-221 as an important regulatory node through which tip cell migration and proliferation are controlled during angiogenesis.Source
Dev Cell. 2012 Feb 14;22(2):418-29. Link to article on publisher's siteDOI
10.1016/j.devcel.2012.01.008Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43970PubMed ID
22340502Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.devcel.2012.01.008