PUBLICATION

Plexind1 negatively regulates zebrafish lymphatic development

Authors
Britto, D.D., He, J., Misa, J.P., Chen, W., Kakadia, P.M., Grimm, L., Herbert, C.D., Crosier, K.E., Crosier, P.S., Bohlander, S.K., Hogan, B.M., Hall, C.J., Torres-Vázquez, J., Astin, J.W.
ID
ZDB-PUB-221008-3
Date
2022
Source
Development (Cambridge, England)   149(21): (Journal)
Registered Authors
Astin, Jonathan, Chen, Wenxuan, Crosier, Kathy, Crosier, Phil, Herbert, Caitlin, Hogan, Ben M.
Keywords
Guidance, Lymphangiogenesis, Lymphatic, Plexind1, Zebrafish
MeSH Terms
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Endothelial Cells/metabolism
  • Lymphatic Vessels*/metabolism
  • Carrier Proteins/metabolism
  • Lymphangiogenesis/genetics
  • Animals
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Receptors, Cell Surface/genetics
  • Receptors, Cell Surface/metabolism
  • Semaphorins*/genetics
  • Semaphorins*/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
(all 15)
PubMed
36205097 Full text @ Development
Abstract
Lymphangiogenesis is a dynamic process that involves the directed migration of lymphatic endothelial cells (LECs) to form lymphatic vessels. The molecular mechanisms that underpin lymphatic vessel patterning are not fully elucidated and, to date, no global regulator of lymphatic vessel guidance is known. In this study, we identify the transmembrane cell signalling receptor Plexind1 as a negative regulator of both lymphatic vessel guidance and lymphangiogenesis in zebrafish. plxnd1 is expressed in developing lymphatics and is required for the guidance of both the trunk and facial lymphatic networks. Loss of plxnd1 is associated with misguided intersegmental lymphatic vessel growth and aberrant facial lymphatic branches. Lymphatic guidance in the trunk is mediated, at least in part, by the Plxnd1 ligands, Semaphorin3aa and Semaphorin3c. Finally, we show that Plxnd1 normally antagonises Vegfr/Erk signalling to ensure the correct number of facial LECs and that loss of plxnd1 results in facial lymphatic hyperplasia. As a global negative regulator of lymphatic vessel development, the Sema/Plxnd1 signalling pathway is a potential therapeutic target to treat diseases associated with dysregulated lymphatic growth.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
nz101Tg/nz101Tg; s843Tg/s843Tg + MO2-plxnd1standard conditionsDay 6
nz101Tg/nz101Tg; s843Tg/s843Tg + MO2-plxnd1standard conditionsDay 6
nz101Tg/nz101Tg; s843Tg/s843Tg + MO2-plxnd1standard conditionsDay 6
nz101Tg/nz101Tg; s843Tg/s843Tg + MO2-plxnd1standard conditionsDay 6
nz101Tg/nz101Tg; y7Tg/y7Tg + MO1-vegfdstandard conditionsDay 6
nz101Tg/nz101Tg; y7Tg/y7Tg + MO2-plxnd1standard conditionsPrim-25
nz101Tg/nz101Tg; y7Tg/y7Tg + MO2-plxnd1standard conditionsProtruding-mouth
nz150Tg/nz150Tg; y7Tg/y7Tg + MO2-plxnd1standard conditionsProtruding-mouth to Day 6
plxnd1fov01b/+; plxnd1nz75/+; nz101Tg/nz101Tg; s843Tg/s843Tgstandard conditionsDay 6
plxnd1fov01b/+; plxnd1nz75/+; nz101Tg/nz101Tg; s843Tg/s843Tgstandard conditionsDay 6
1 - 10 of 30
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fov01b
    Point Mutation
    la4TgTransgenic Insertion
      nz49TgTransgenic Insertion
        nz75
          Point Mutation
          nz101TgTransgenic Insertion
            nz150TgTransgenic Insertion
              s843TgTransgenic Insertion
                sa10241
                  Point Mutation
                  sa15161
                    Point Mutation
                    uq3bhTgTransgenic Insertion
                      1 - 10 of 13
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      flt1MO5-flt1MRPHLNO
                      plxnd1MO2-plxnd1MRPHLNO
                      vegfdMO1-vegfdMRPHLNO
                      1 - 3 of 3
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                      Fish
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab9-mapkmonoclonal
                        IgGRabbit
                        1 - 1 of 1
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                        Orthology
                        No data available
                        Engineered Foreign Genes
                        Marker Marker Type Name
                        DsRedEFGDsRed
                        EGFPEFGEGFP
                        KALTA4EFGKALTA4
                        mCherryEFGmCherry
                        RFPEFGRFP
                        VenusEFGVenus
                        1 - 6 of 6
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                        Mapping
                        No data available