PUBLICATION

Localised Collagen2a1 secretion supports lymphatic endothelial cell migration in the zebrafish embryo

Authors
Chaudhury, S., Okuda, K.S., Koltowska, K., Lagendijk, A.K., Paterson, S., Baillie, G.J., Simons, C., Smith, K.A., Hogan, B.M., Bower, N.I.
ID
ZDB-PUB-200826-3
Date
2020
Source
Development (Cambridge, England)   147(18): (Journal)
Registered Authors
Hogan, Ben M., Okuda, Kazuhide Shaun, Paterson, Scott, Smith, Kelly
Keywords
Col2a1, Collagen, Extracellular matrix, Lymphangiogenesis, Mbtps1, Sec23a, Zebrafish
MeSH Terms
  • Embryo, Mammalian/metabolism*
  • Veins/metabolism
  • Endothelial Cells/metabolism*
  • Lymphangiogenesis/physiology
  • Animals
  • Morphogenesis/physiology
  • Cell Communication/physiology
  • Zebrafish/metabolism*
  • Cell Proliferation/physiology
  • Lymphatic Vessels/metabolism*
  • Cell Movement/physiology*
  • Collagen Type II/metabolism*
(all 12)
PubMed
32839180 Full text @ Development
Abstract
The lymphatic vasculature develops primarily from pre-existing veins. A pool of lymphatic endothelial cells (LECs) first sprout from cardinal veins followed by migration and proliferation to colonise embryonic tissues. While much is known about the molecular regulation of LEC fate and sprouting during early lymphangiogenesis, we know far less about the instructive and permissive signals that support LEC migration through the embryo. Using a forward genetic screen, we identified mbtps1 and sec23a, components of the COP-II protein secretory pathway, as essential for developmental lymphangiogenesis. In both mutants, LECs initially depart the cardinal vein but then fail in their ongoing migration. A key cargo that failed to be secreted in both mutants was a type II collagen (Col2a1). Col2a1 is normally secreted by notochord sheath cells alongside which LECs migrate. col2a1a mutants displayed defects in the migratory behaviour of LECs and failed lymphangiogenesis. These studies thus identify Col2a1 as a key cargo secreted by notochord sheath cells and required for the migration of LECs. These findings combine with our current understanding to suggest that successive cell-to-cell and cell-matrix interactions regulate the migration of LECs through the embryonic environment during development.
Genes / Markers
Figures
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Expression
Phenotype
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
nz101TgTransgenic Insertion
    s843TgTransgenic Insertion
      uq22bh
        Point Mutation
        uq23bh
          Small Deletion
          uq27bh
            Point Mutation
            uq28bh
              Insertion
              uq36bh
                Indel
                y7TgTransgenic Insertion
                  1 - 8 of 8
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                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  col2a1aCRISPR1-col2a1aCRISPR
                  mbtps1CRISPR1-mbtps1CRISPR
                  sec23aCRISPR1-sec23aCRISPR
                  1 - 3 of 3
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                  Fish
                  Antibodies
                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  DsRedEFGDsRed
                  EGFPEFGEGFP
                  1 - 2 of 2
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                  Mapping
                  No data available