PUBLICATION

Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting

Authors
Watterston, C., Halabi, R., McFarlane, S., Childs, S.J.
ID
ZDB-PUB-210824-16
Date
2021
Source
PLoS Genetics   17: e1009769 (Journal)
Registered Authors
Childs, Sarah J., Halabi, Rami, McFarlane, Sarah
Keywords
none
MeSH Terms
  • Vascular Endothelial Growth Factors/metabolism
  • Vascular Endothelial Growth Factors/pharmacology
  • Membrane Proteins/metabolism
  • Semaphorins/genetics
  • Semaphorins/metabolism*
  • Morphogenesis
  • Signal Transduction/physiology
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Animals
  • Cell Movement
  • Endothelial Cells/metabolism
  • Endothelium/metabolism
  • Vascular Endothelial Growth Factor Receptor-1
  • Receptors, Notch/metabolism
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/metabolism*
  • Neovascularization, Physiologic/genetics*
  • Neovascularization, Physiologic/physiology
(all 21)
PubMed
34424892 Full text @ PLoS Genet.
Abstract
Vessel growth integrates diverse extrinsic signals with intrinsic signaling cascades to coordinate cell migration and sprouting morphogenesis. The pro-angiogenic effects of Vascular Endothelial Growth Factor (VEGF) are carefully controlled during sprouting to generate an efficiently patterned vascular network. We identify crosstalk between VEGF signaling and that of the secreted ligand Semaphorin 3fb (Sema3fb), one of two zebrafish paralogs of mammalian Sema3F. The sema3fb gene is expressed by endothelial cells in actively sprouting vessels. Loss of sema3fb results in abnormally wide and stunted intersegmental vessel artery sprouts. Although the sprouts initiate at the correct developmental time, they have a reduced migration speed. These sprouts have persistent filopodia and abnormally spaced nuclei suggesting dysregulated control of actin assembly. sema3fb mutants show simultaneously higher expression of pro-angiogenic (VEGF receptor 2 (vegfr2) and delta-like 4 (dll4)) and anti-angiogenic (soluble VEGF receptor 1 (svegfr1)/ soluble Fms Related Receptor Tyrosine Kinase 1 (sflt1)) pathway components. We show increased phospho-ERK staining in migrating angioblasts, consistent with enhanced Vegf activity. Reducing Vegfr2 kinase activity in sema3fb mutants rescues angiogenic sprouting. Our data suggest that Sema3fb plays a critical role in promoting endothelial sprouting through modulating the VEGF signaling pathway, acting as an autocrine cue that modulates intrinsic growth factor signaling.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ca304
    		Small Deletion
    ca305
      		Small Deletion
      ci5TgTransgenic Insertion
        y7TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          sema3fbMO1-sema3fbMRPHLNO
          tnnt2aMO1-tnnt2aMRPHLNO
          1 - 2 of 2
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          Fish
          No data available
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          mCherryEFGmCherry
          1 - 2 of 2
          Show
          Mapping
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          Citation
          Watterston, C., Halabi, R., McFarlane, S., Childs, S.J. (2021) Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting. PLoS Genetics. 17:e1009769.