Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis

Jessica E. Nesmith, John C. Chappell, Julia G. Cluceru, Victoria L. Bautch

Research output: Research - peer-reviewArticle

  • 4 Citations

Abstract

Blood vessel formation is essential for vertebrate development and is primarily achieved by angiogenesis - endothelial cell sprouting from pre-existing vessels. Vessel networks expand when sprouts form new connections, a process whose regulation is poorly understood. Here, we show that vessel anastomosis is spatially regulated by Flt1 (VEGFR1), a VEGFA receptor that acts as a decoy receptor. In vivo, expanding vessel networks favor interactions with Flt1 mutant mouse endothelial cells. Live imaging in human endothelial cells in vitro revealed that stable connections are preceded by transient contacts from extending sprouts, suggesting sampling of potential target sites, and lowered Flt1 levels reduced transient contacts and increased VEGFA signaling. Endothelial cells at target sites with reduced Flt1 and/or elevated protrusive activity were more likely to form stable connections with incoming sprouts. Target cells with reduced membrane-localized Flt1 (mFlt1), but not soluble Flt1, recapitulated the bias towards stable connections, suggesting that relative mFlt1 expression spatially influences the selection of stable connections. Thus, sprout anastomosis parameters are regulated by VEGFA signaling, and stable connections are spatially regulated by endothelial cell-intrinsic modulation of mFlt1, suggesting new ways to manipulate vessel network formation.

LanguageEnglish (US)
Pages869-889
Number of pages21
JournalDevelopment (Cambridge)
Volume144
Issue number5
DOIs
StatePublished - Mar 1 2017

Fingerprint

vessel
blood
Blood Vessels
Endothelial Cells
contact
Membranes
membrane
regulation
trend
interaction
Vertebrates
In Vitro Techniques
vertebrate
sampling
mutant
parameter

Keywords

  • Anastomosis
  • Angiogenesis
  • Endothelial cells
  • Flt1 isoforms
  • VEGF-A
  • VEGFR1

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis. / Nesmith, Jessica E.; Chappell, John C.; Cluceru, Julia G.; Bautch, Victoria L.

In: Development (Cambridge), Vol. 144, No. 5, 01.03.2017, p. 869-889.

Research output: Research - peer-reviewArticle

Nesmith JE, Chappell JC, Cluceru JG, Bautch VL. Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis. Development (Cambridge). 2017 Mar 1;144(5):869-889. Available from, DOI: 10.1242/dev.145672
Nesmith, Jessica E. ; Chappell, John C. ; Cluceru, Julia G. ; Bautch, Victoria L./ Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis. In: Development (Cambridge). 2017 ; Vol. 144, No. 5. pp. 869-889
@article{93c0582e97d74b14b97a388012462895,
title = "Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis",
abstract = "Blood vessel formation is essential for vertebrate development and is primarily achieved by angiogenesis - endothelial cell sprouting from pre-existing vessels. Vessel networks expand when sprouts form new connections, a process whose regulation is poorly understood. Here, we show that vessel anastomosis is spatially regulated by Flt1 (VEGFR1), a VEGFA receptor that acts as a decoy receptor. In vivo, expanding vessel networks favor interactions with Flt1 mutant mouse endothelial cells. Live imaging in human endothelial cells in vitro revealed that stable connections are preceded by transient contacts from extending sprouts, suggesting sampling of potential target sites, and lowered Flt1 levels reduced transient contacts and increased VEGFA signaling. Endothelial cells at target sites with reduced Flt1 and/or elevated protrusive activity were more likely to form stable connections with incoming sprouts. Target cells with reduced membrane-localized Flt1 (mFlt1), but not soluble Flt1, recapitulated the bias towards stable connections, suggesting that relative mFlt1 expression spatially influences the selection of stable connections. Thus, sprout anastomosis parameters are regulated by VEGFA signaling, and stable connections are spatially regulated by endothelial cell-intrinsic modulation of mFlt1, suggesting new ways to manipulate vessel network formation.",
keywords = "Anastomosis, Angiogenesis, Endothelial cells, Flt1 isoforms, VEGF-A, VEGFR1",
author = "Nesmith, {Jessica E.} and Chappell, {John C.} and Cluceru, {Julia G.} and Bautch, {Victoria L.}",
year = "2017",
month = "3",
doi = "10.1242/dev.145672",
volume = "144",
pages = "869--889",
journal = "Development",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "5",

}

TY - JOUR

T1 - Blood vessel anastomosis is spatially regulated by Flt1 during angiogenesis

AU - Nesmith,Jessica E.

AU - Chappell,John C.

AU - Cluceru,Julia G.

AU - Bautch,Victoria L.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Blood vessel formation is essential for vertebrate development and is primarily achieved by angiogenesis - endothelial cell sprouting from pre-existing vessels. Vessel networks expand when sprouts form new connections, a process whose regulation is poorly understood. Here, we show that vessel anastomosis is spatially regulated by Flt1 (VEGFR1), a VEGFA receptor that acts as a decoy receptor. In vivo, expanding vessel networks favor interactions with Flt1 mutant mouse endothelial cells. Live imaging in human endothelial cells in vitro revealed that stable connections are preceded by transient contacts from extending sprouts, suggesting sampling of potential target sites, and lowered Flt1 levels reduced transient contacts and increased VEGFA signaling. Endothelial cells at target sites with reduced Flt1 and/or elevated protrusive activity were more likely to form stable connections with incoming sprouts. Target cells with reduced membrane-localized Flt1 (mFlt1), but not soluble Flt1, recapitulated the bias towards stable connections, suggesting that relative mFlt1 expression spatially influences the selection of stable connections. Thus, sprout anastomosis parameters are regulated by VEGFA signaling, and stable connections are spatially regulated by endothelial cell-intrinsic modulation of mFlt1, suggesting new ways to manipulate vessel network formation.

AB - Blood vessel formation is essential for vertebrate development and is primarily achieved by angiogenesis - endothelial cell sprouting from pre-existing vessels. Vessel networks expand when sprouts form new connections, a process whose regulation is poorly understood. Here, we show that vessel anastomosis is spatially regulated by Flt1 (VEGFR1), a VEGFA receptor that acts as a decoy receptor. In vivo, expanding vessel networks favor interactions with Flt1 mutant mouse endothelial cells. Live imaging in human endothelial cells in vitro revealed that stable connections are preceded by transient contacts from extending sprouts, suggesting sampling of potential target sites, and lowered Flt1 levels reduced transient contacts and increased VEGFA signaling. Endothelial cells at target sites with reduced Flt1 and/or elevated protrusive activity were more likely to form stable connections with incoming sprouts. Target cells with reduced membrane-localized Flt1 (mFlt1), but not soluble Flt1, recapitulated the bias towards stable connections, suggesting that relative mFlt1 expression spatially influences the selection of stable connections. Thus, sprout anastomosis parameters are regulated by VEGFA signaling, and stable connections are spatially regulated by endothelial cell-intrinsic modulation of mFlt1, suggesting new ways to manipulate vessel network formation.

KW - Anastomosis

KW - Angiogenesis

KW - Endothelial cells

KW - Flt1 isoforms

KW - VEGF-A

KW - VEGFR1

UR - http://www.scopus.com/inward/record.url?scp=85016129089&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016129089&partnerID=8YFLogxK

U2 - 10.1242/dev.145672

DO - 10.1242/dev.145672

M3 - Article

VL - 144

SP - 869

EP - 889

JO - Development

T2 - Development

JF - Development

SN - 0950-1991

IS - 5

ER -