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Regulation of Angiogenesis and Blood Supply

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Related Experiment Video

Updated: May 18, 2026

In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
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Published on: May 11, 2021

S1P1 inhibits sprouting angiogenesis during vascular development.

Adi Ben Shoham1, Guy Malkinson, Sharon Krief

  • 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.

Development (Cambridge, England)
|September 7, 2012
PubMed
Summary

Sphingosine-1-phosphate receptor 1 (S1P(1)) inhibits excessive sprouting during blood vessel development. This finding reveals a new feedback loop regulating angiogenesis, crucial for embryonic vascular formation.

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2.5D Model for Ex Vivo Mechanical Characterization of Sprouting Angiogenesis in Living Tissue
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In Vitro Three-Dimensional Sprouting Assay of Angiogenesis Using Mouse Embryonic Stem Cells for Vascular Disease Modeling and Drug Testing
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2.5D Model for Ex Vivo Mechanical Characterization of Sprouting Angiogenesis in Living Tissue

Published on: February 28, 2025

Area of Science:

  • Developmental Biology
  • Vascular Biology
  • Molecular Biology

Background:

  • Embryonic development requires precise coordination between the vascular system and organogenesis.
  • Sprouting angiogenesis drives vascular expansion, but mechanisms ensuring neovessel stability are unclear.
  • Sphingosine-1-phosphate receptor 1 (S1P(1)) is implicated in vascular maturation and previously considered pro-angiogenic.

Purpose of the Study:

  • To investigate the role of S1P(1) in regulating sprouting angiogenesis.
  • To determine if S1P(1) acts independently of mural cells in controlling neovessel formation.
  • To elucidate the interaction between S1P(1) and vascular endothelial growth factor A (Vegfa) in vascular development.

Main Methods:

  • Analysis of S1P(1)-null mouse embryos to observe vascular development.
  • Conditional blocking of S1P(1) expression specifically in endothelial cells (ECs).
  • Knockdown studies in zebrafish embryos to assess cross-species conservation.
  • Genetic interaction studies between S1P(1) and Vegfa.

Main Results:

  • S1P(1)-null embryos exhibit severe vascular aberrations, including excessive sprouting, indicating an anti-angiogenic role.
  • S1P(1) functions autonomously in ECs to negatively regulate sprouting angiogenesis.
  • Similar phenotypes in zebrafish and EC-specific S1P(1) knockdown confirm its conserved, EC-autonomous function.
  • S1P(1) genetically interacts with Vegfa, with Vegfa promoting and S1P(1) inhibiting sprouting.

Conclusions:

  • S1P(1) is an EC-autonomous anti-angiogenic factor that prevents excessive sprouting and neovessel fusion.
  • Blood-borne S1P acting through S1P(1) provides a negative feedback mechanism to inhibit angiogenesis once a vascular bed is functional.
  • This discovery reveals a novel regulatory pathway for angiogenesis essential for proper vascular development.