PUBLICATION

Specific fibroblast subpopulations and neuronal structures provide local sources of Vegfc-processing components during zebrafish lymphangiogenesis

Authors
Wang, G., Muhl, L., Padberg, Y., Dupont, L., Peterson-Maduro, J., Stehling, M., le Noble, F., Colige, A., Betsholtz, C., Schulte-Merker, S., van Impel, A.
ID
ZDB-PUB-200603-12
Date
2020
Source
Nature communications   11: 2724 (Journal)
Registered Authors
Betsholtz, Christer, le Noble, Ferdinand, Peterson-Maduroe, Josi, Schulte-Merker, Stefan, van Impel, Andreas
Keywords
none
Datasets
GEO:GSE146923
MeSH Terms
  • Neurons/metabolism*
  • ADAMTS Proteins/genetics
  • ADAMTS Proteins/metabolism
  • Animals, Genetically Modified
  • Vascular Endothelial Growth Factor C/genetics*
  • Vascular Endothelial Growth Factor C/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Fibroblasts/metabolism*
  • Microscopy, Confocal
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Animals
  • Humans
  • Gene Expression Regulation, Developmental
  • Lymphatic Vessels/embryology
  • Lymphatic Vessels/metabolism
  • Procollagen N-Endopeptidase/genetics
  • Procollagen N-Endopeptidase/metabolism
  • Lymphangiogenesis/genetics*
  • HEK293 Cells
(all 22)
PubMed
32483144 Full text @ Nat. Commun.
Abstract
Proteolytical processing of the growth factor VEGFC through the concerted activity of CCBE1 and ADAMTS3 is required for lymphatic development to occur. How these factors act together in time and space, and which cell types produce these factors is not understood. Here we assess the function of Adamts3 and the related protease Adamts14 during zebrafish lymphangiogenesis and show both proteins to be able to process Vegfc. Only the simultaneous loss of both protein functions results in lymphatic defects identical to vegfc loss-of-function situations. Cell transplantation experiments demonstrate neuronal structures and/or fibroblasts to constitute cellular sources not only for both proteases but also for Ccbe1 and Vegfc. We further show that this locally restricted Vegfc maturation is needed to trigger normal lymphatic sprouting and directional migration. Our data provide a single-cell resolution model for establishing secretion and processing hubs for Vegfc during developmental lymphangiogenesis.
Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu5333TgTransgenic Insertion
    hu6635TgTransgenic Insertion
      hu6741TgTransgenic Insertion
        hu7135TgTransgenic Insertion
          hu8876TgTransgenic Insertion
            hu9228TgTransgenic Insertion
              hu10891
                Small Deletion
                hu11198
                  Small Deletion
                  hu11300
                    Small Deletion
                    hu11304
                      Small Deletion
                      1 - 10 of 20
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      1 - 5 of 5
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                      Fish
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CitrineEFGCitrine
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GAL4FFEFGGAL4FF
                      GFPEFGGFP
                      mCherryEFGmCherry
                      mTurquoiseEFGmTurquoise
                      RFPEFGRFP
                      1 - 8 of 8
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                      Mapping
                      No data available