Sema3F (Semaphorin 3F) Selectively Drives an Extraembryonic Proangiogenic Program

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 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.Arteriosclerosis, Thrombosis, and Vascular Biology is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

Original languageEnglish
JournalArteriosclerosis, Thrombosis, and Vascular Biology
DOIs
Publication statusAccepted/In press - Jul 20 2017

Fingerprint

Semaphorins
Yolk Sac
Blood Vessels
MicroRNAs
Thrombospondin 1
Epithelial Cells
Phosphorylation
Embryonal Carcinoma Stem Cells
Aptitude
Arteriosclerosis
Licensure
Morphogenesis
Placenta
Vascular Endothelial Growth Factor A
Cues
Reproduction
Vertebrates
Thrombosis
Transcription Factors
Endothelial Cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{f9d548f335ff413f8b55992aab2f196c,
title = "Sema3F (Semaphorin 3F) Selectively Drives an Extraembryonic Proangiogenic Program",
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 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.Arteriosclerosis, Thrombosis, and Vascular Biology is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.",
author = "Donatella Regano and Alessia Visintin and Fabiana Clapero and Federico Bussolino and Donatella Valdembri and Federica Maione and Guido Serini and Enrico Giraudo",
year = "2017",
month = "7",
day = "20",
doi = "10.1161/ATVBAHA.117.308226",
language = "English",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - Sema3F (Semaphorin 3F) Selectively Drives an Extraembryonic Proangiogenic Program

AU - Regano, Donatella

AU - Visintin, Alessia

AU - Clapero, Fabiana

AU - Bussolino, Federico

AU - Valdembri, Donatella

AU - Maione, Federica

AU - Serini, Guido

AU - Giraudo, Enrico

PY - 2017/7/20

Y1 - 2017/7/20

N2 - 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 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.Arteriosclerosis, Thrombosis, and Vascular Biology is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

AB - 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 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.Arteriosclerosis, Thrombosis, and Vascular Biology is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.

UR - http://www.scopus.com/inward/record.url?scp=85025428337&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85025428337&partnerID=8YFLogxK

U2 - 10.1161/ATVBAHA.117.308226

DO - 10.1161/ATVBAHA.117.308226

M3 - Article

AN - SCOPUS:85025428337

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

ER -