PUBLICATION

Divergence of zebrafish and mouse lymphatic cell fate specification pathways

Authors
van Impel, A., Zhao, Z., Hermkens, D.M., Roukens, M.G., Fischer, J.C., Peterson-Maduro, J., Duckers, H., Ober, E.A., Ingham, P.W., and Schulte-Merker, S.
ID
ZDB-PUB-140502-14
Date
2014
Source
Development (Cambridge, England)   141(6): 1228-1238 (Journal)
Registered Authors
Fischer, Johanna, Ingham, Philip, Ober, Elke, Peterson-Maduroe, Josi, Schulte-Merker, Stefan, van Impel, Andreas, Zhao, Zhonghua
Keywords
Coup-TFII, Lymphangiogenesis, Nr2f2, Prox1, Sox18
MeSH Terms
  • Animals, Genetically Modified
  • SOXF Transcription Factors/deficiency
  • SOXF Transcription Factors/genetics
  • SOXF Transcription Factors/metabolism
  • Cell Lineage
  • Mice
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism
  • Mutation
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/physiology*
  • Animals
  • Lymphatic Vessels/cytology
  • Lymphatic Vessels/metabolism
  • COUP Transcription Factor II/deficiency
  • COUP Transcription Factor II/genetics
  • COUP Transcription Factor II/metabolism
  • Species Specificity
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/physiology
  • Cell Differentiation
  • Lymphangiogenesis/genetics
  • Lymphangiogenesis/physiology*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
  • Gene Expression Regulation, Developmental
  • Tumor Suppressor Proteins/deficiency
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/physiology*
  • Mice, Knockout
(all 33)
PubMed
24523456 Full text @ Development
Abstract

In mammals, the homeodomain transcription factor Prox1 acts as the central regulator of lymphatic cell fate. Its restricted expression in a subset of cardinal vein cells leads to a switch towards lymphatic specification and hence represents a prerequisite for the initiation of lymphangiogenesis. Murine Prox1-null embryos lack lymphatic structures, and sustained expression of Prox1 is indispensable for the maintenance of lymphatic cell fate even at adult stages, highlighting the unique importance of this gene for the lymphatic lineage. Whether this pre-eminent role of Prox1 within the lymphatic vasculature is conserved in other vertebrate classes has remained unresolved, mainly owing to the lack of availability of loss-of-function mutants. Here, we re-examine the role of Prox1a in zebrafish lymphangiogenesis. First, using a transgenic reporter line, we show that prox1a is initially expressed in different endothelial compartments, becoming restricted to lymphatic endothelial cells only at later stages. Second, using targeted mutagenesis, we show that Prox1a is dispensable for lymphatic specification and subsequent lymphangiogenesis in zebrafish. In line with this result, we found that the functionally related transcription factors Coup-TFII and Sox18 are also dispensable for lymphangiogenesis. Together, these findings suggest that lymphatic commitment in zebrafish and mice is controlled in fundamentally different ways.

Genes / Markers
Figures
Figure Gallery (9 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu5333TgTransgenic Insertion
    hu7135TgTransgenic Insertion
      hu9236TgTransgenic Insertion
        hu10320
          Insertion
          hu10330
            Insertion
            i278
              Small Deletion
              nim5TgTransgenic Insertion
                s916TgTransgenic Insertion
                  sa35
                    Point Mutation
                    y1TgTransgenic Insertion
                      1 - 10 of 10
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      nr2f2TALEN1-nr2f2TALEN
                      sox18TALEN1-sox18TALEN
                      1 - 2 of 2
                      Show
                      Fish
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CitrineEFGCitrine
                      EGFPEFGEGFP
                      GAL4FFEFGGAL4FF
                      KALTA4EFGKALTA4
                      mCherryEFGmCherry
                      RFPEFGRFP
                      TagRFPEFGTagRFP
                      1 - 7 of 7
                      Show
                      Mapping
                      No data available