Sema3F (Semaphorin 3F) Selectively Drives an Extraembryonic Proangiogenic Program. Issue 9 (September 2017)

• Record Type: Journal Article
• Authors: Regano, Donatella; Visintin, Alessia; Clapero, Fabiana; Bussolino, Federico; Valdembri, Donatella; Maione, Federica; Serini, Guido; Giraudo, Enrico
• Is Part Of: Arteriosclerosis, thrombosis, and vascular biology. Volume 37:Issue 9(2017)
• Publication Date: 2017-09
• Subjects: angiogenesis modulating agents -- mice -- myc -- semaphorins -- thrombospondins -- yolk sac; Arteriosclerosis -- Periodicals; Thrombosis -- Periodicals; Blood-vessels -- Pathophysiology -- Periodicals; Electronic journals; 616.13
• DOI: 10.1161/ATVBAHA.117.308226
• Languages: English
• ISSNs: 1079-5642

Abstract

Abstract : Objective—: Molecular pathways governing blood vessel patterning are vital to vertebrate development. Because of their ability to counteract proangiogenic factors, antiangiogenic secreted Sema3 (class 3 semaphorins) control embryonic vascular morphogenesis. However, if and how Sema3 may play a role in the control of extraembryonic vascular development is presently unknown. Approach and Results—: By characterizing genetically modified mice, here, we show that surprisingly Sema3F acts instead as a selective extraembryonic, but not intraembryonic proangiogenic cue. Both in vivo and in vitro, in visceral yolk sac epithelial cells, Sema3F signals to inhibit the phosphorylation-dependent degradation of Myc, a transcription factor that drives the expression of proangiogenic genes, such as the microRNA cluster 17/92. In Sema3f -null yolk sacs, the transcription of Myc-regulated microRNA 17/92 cluster members is impaired, and the synthesis of Myc and microRNA 17/92 foremost antiangiogenic target Thbs1 (thrombospondin 1) is increased, whereas Vegf (vascular endothelial growth factor) signaling is inhibited in yolk sac endothelial cells. Consistently, exogenous recombinant Sema3F inhibits the phosphorylation-dependent degradation of Myc and the synthesis of Thbs1 in mouse F9 teratocarcinoma stem cells that were in vitro differentiated in visceral yolk sac epithelial cells. Sema3f −/− mice placentas are also highly anemic and abnormally vascularized. Conclusions—: Sema3F functions as an unconventional Sema3 that promotes extraembryonic angiogenesis by inhibiting the Myc-regulated synthesis of Thbs1 in visceral yolk sac epithelial cells. Abstract : Supplemental Digital Content is available in the text.