PUBLICATION

Determination of Endothelial Stalk versus Tip Cell Potential during Angiogenesis by H2.0-like Homeobox-1

Authors
Herbert, S.P., Cheung, J.Y., and Stainier, D.Y.
ID
ZDB-PUB-120830-18
Date
2012
Source
Current biology : CB   22(19): 1789-1794 (Journal)
Registered Authors
Herbert, Shane, Stainier, Didier
Keywords
none
Datasets
GEO:GSE130889
MeSH Terms
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Microfilament Proteins/genetics
  • Microfilament Proteins/metabolism
  • Embryo, Nonmammalian
  • Vascular Endothelial Growth Factor Receptor-3/genetics
  • Vascular Endothelial Growth Factor Receptor-3/metabolism
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Gene Expression Regulation, Developmental
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Neovascularization, Physiologic/physiology*
  • Animals, Genetically Modified
  • Muscle Proteins/genetics
  • Muscle Proteins/metabolism
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism*
  • Animals
  • Endothelial Cells/metabolism
  • Blood Vessels/cytology*
  • Blood Vessels/embryology*
  • Vascular Endothelial Growth Factor A/metabolism
(all 23)
PubMed
22921365 Full text @ Curr. Biol.
Abstract

Tissue branching morphogenesis requires the hierarchical organization of sprouting cells into leading “tip” and trailing “stalk” cells [ [1] and [2]]. During new blood vessel branching (angiogenesis), endothelial tip cells (TCs) lead sprouting vessels, extend filopodia, and migrate in response to gradients of the secreted ligand, vascular endothelial growth factor (Vegf) [3]. In contrast, adjacent stalk cells (SCs) trail TCs, generate the trunk of new vessels, and critically maintain connectivity with parental vessels. Here, we establish that h2.0-like homeobox-1 (Hlx1) determines SC potential, which is critical for angiogenesis during zebrafish development. By combining a novel pharmacological strategy for the manipulation of angiogenic cell behavior in vivo with transcriptomic analyses of sprouting cells, we identify the uniquely sprouting-associated gene, hlx1. Expression of hlx1 is almost entirely restricted to sprouting endothelial cells and is excluded from adjacent nonangiogenic cells. Furthermore, Hlx1 knockdown reveals its essential role in angiogenesis. Importantly, mosaic analyses uncover a cell-autonomous role for Hlx1 in the maintenance of SC identity in sprouting vessels. Hence, Hlx1-mediated maintenance of SC potential regulates angiogenesis, a finding that may have novel implications for sprouting morphogenesis of other tissues.

Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s5
    Point Mutation
    s843TgTransgenic Insertion
      sd2TgTransgenic Insertion
        ubs1TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          flt4MO1-flt4MRPHLNO
          hlx1MO1-hlx1MRPHLNO
          hlx1MO2-hlx1MRPHLNO
          1 - 3 of 3
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          Fish
          Antibodies
          No data available
          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