Details

Autor(en) / Beteiligte

• Nicoli, Stefania
• Knyphausen, Carl-Philipp
• Zhu, Lihua J.
• Lakshmanan, Abirami
• Lawson, Nathan D.

Titel

miR-221 Is Required for Endothelial Tip Cell Behaviors during Vascular Development

Ist Teil von

• Developmental cell, 2012-02, Vol.22 (2), p.418-429

Ort / Verlag

Cambridge, MA: Elsevier Inc

Erscheinungsjahr

2012

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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. [Display omitted] ► Deep sequencing reveals microRNAs essential for zebrafish vascular development ► miR-221 is required for angiogenesis and acts in the Vegfc/Flt4 signaling pathway ► miR-221 acts autonomously to promote endothelial tip cell migration and proliferation ► miR-221 targets cdkn1b and pik3r1 to induce proliferation and PI3K output Angiogenesis requires coordination of distinct cell behaviors between sprouting tip cells and the stalk cells connected to the patent circulatory system. Nicoli et al. identify a microRNA, miR-221, that is required for tip cell migration and proliferation through the repression of targets involved in PI3K signaling and cell cycle inhibition.