NRP1 acts cell autonomously in endothelium to promote tip cell function during sprouting angiogenesis. (Blood, 2013, 121: 2352-2362)

報告日期: 2014/11/04
報告時間: 4:00/4:50
報告學生: 黃家葳(以英文報告)
講評老師: 陳玉玲
附件下載: 下載[1438-1412237943-1.pdf] 

NRP1 acts cell autonomously in endothelium to promote tip cell function during sprouting angiogenesis

Alessandro Fantin, Joaquim M. Vieira, Alice Plein, Laura Denti, Marcus Fruttiger, Jeffrey W. Pollard, and Christiana Ruhrberg

Blood. 121, 2352–2362 (2013)

Speaker: Chia-Wei Huang                    Date: 2014/11/04 16:00-16:50

Commentator: Yuh-Ling Chen                Location: Room 602

Abstract

During brain development, the formation of integrated vascular networks is critical for supporting neuron maturation. Neuropilin-1 (NRP1) is found in several cell types which interact both homotypically and heterotypically with endothelial VEGFR2, and enhance the VEGF signaling in the endothelial cells. However, the potential significance of interaction between nonendothelial NRP1 and endothelial cells in regulating angiogenesis is still unclear. Therefore, this paper aimed to investigate whether the endothelial and non-endothelial NRP1 are both essential for the angiogenesis in developing brain, and their role in promoting endothelial functions. The deletion of NRP1 in selective cell type was achieved by using Cre/Lox recombination system which express Cre recombinase under specific promoter. The successful and selective recombination was confirmed by YFP expression in the mutant mice containing the floxed Rosa26yfp reporter which express YFP in Cre active cells. Immunolabeling were performed to observe the expression of NRP1, cell markers, and vascular structure in developing subventricular vascular plexus of mice embryo. Neural progenitors and macrophages showed participated in angiogenesis in developing brain. However, targeting NRP1 in either kind of the cells doesn’t alter the branch point numbers of vascular plexus indicated nonessential role of nonendothelial NRP1 in angiogenesis. NRP1 was also expressed by both tip and stalk cells in endothelium, whereas deletion of endothelial NRP1 significantly disrupted the formation of vascular plexus. Interestingly, the angiogenesis of Cre mediated endothelial NRP1 knockout mice showed less severe than complete NRP1 knockout mice, and showed partially preserved the number of NRP1+ cells. Among the NRP1+ cells, significantly higher percentage of NPR1+/YFP- endothelial cells attained the tip cell position rather than stalk cell indicated that the recombination resistant cells gained the advantage when competing for the tip cell position with NRP1- cells. Taken together, the results suggested that endothelial NRP1 is important in negotiating the tip cell position, and thus boost the sprouting angiogenesis.

 

References

Gerhardt, H., C. et al. (2004). "Neuropilin1 is required for endothelial tip cell guidance in the developing central nervous system." Dev Dynam231(3): 503-509.

 

 

 

 

The deletion of NRP1 in endothelial cells, neural progenitors, and macrophages were achieved by using Cre/Lox recombination system which express cre recombinase under Tie2, nestin, and CSF1 promotor, respectively.