The role of microRNAs in neural stem cell-supported endothelial morphogenesis

There is a close association and reciprocal signaling that occurs between ECs and NSPCs in the neurogenic zones of the adult brain. Recognition of this close relationship has led to the descriptive concept of a "neurovascular niche", where endothelial and neural cells interact with each other, both prior to and throughout their maturation. Cross-talk between the two cell types is involved with differentiation, fate determination, and migration of the NSPCs in vitro and in vivo, both in the normal and injured brain [1-3]. In our previous studies we demonstrated that NSPCs continuously release a pro-angiogenic vascular endothelial growth factor, VEGF, which promotes EC survival and morphogenesis [4].As an essential component of vascular development, endothelial morphogenesis is a complex process involving gene activation and upregulation of specific cell signaling pathways. Novel mechanisms regulating gene expression were unveiled following the discovery of microRNAs, which are single-stranded noncoding short (18-24 nucleotides long) RNAs. It is now estimated that up to one-third of encoded genes are regulated by miRNAs, which bind to their mRNA target at complementary sequences in order to downregulate gene expression by inhibiting the mRNA translation into proteins or by inducing mRNA degradation [5]. Recent findings demonstrate that miRNAs control neurogenesis [6,7] and could also help regulate the morphogenesis of endothelial cells [8,9]. However, the role of miRNAs in EC function currently remains unclear, and only a few specific miRNAs targeting endothelial cell function and angiogenesis have been identified. miRNAs including the mir-let-7 family, as well as mir-21, mir-126, mir-221, and mir-222 are highly expressed in endothelial cells [9,10]. Studies have shown that Dicer and Drosha, the RNase III endonucleases involved in miRNA generation, significantly affect angiogenesis [10,11]. Among identified angiogenesis promoters is the miRNA cluster, miR-17-92 [12].