PUBLICATION

S1pr2/G?13 signaling controls myocardial migration by regulating endoderm convergence

Authors
Ye, D., and Lin, F.
ID
ZDB-PUB-130124-24
Date
2013
Source
Development (Cambridge, England)   140(4): 789-799 (Journal)
Registered Authors
Lin, Fang
Keywords
none
MeSH Terms
  • Cell Movement/physiology*
  • Time-Lapse Imaging
  • GTP-Binding Protein alpha Subunits, G12-G13/metabolism*
  • Receptors, Lysosphingolipid/metabolism*
  • Signal Transduction/physiology*
  • Morpholinos/genetics
  • In Situ Hybridization
  • Fluorescent Antibody Technique
  • Animals
  • Endoderm/embryology*
  • Heart/embryology*
  • Myocardium/cytology*
  • Zebrafish/embryology*
(all 13)
PubMed
23318642 Full text @ Development
Abstract

A key process during vertebrate heart development is the migration of bilateral populations of myocardial precursors towards the midline to form the primitive heart tube. In zebrafish, signaling mediated by sphingosine-1-phosphate (S1P) and its cognate G protein-coupled receptor (S1pr2/Mil) is essential for myocardial migration, but the underlying mechanisms remain undefined. Here, we show that suppression of Gα13 signaling disrupts myocardial migration, leading to the formation of two bilaterally located hearts (cardia bifida). Genetic studies indicate that Gα13 acts downstream of S1pr2 to regulate myocardial migration through a RhoGEF-dependent pathway. Furthermore, disrupting any component of the S1pr2/Gα13/RhoGEF pathway impairs endoderm convergence during segmentation, and the endodermal defects correlate with the extent of cardia bifida. Moreover, endoderm transplantation reveals that the presence of wild-type anterior endodermal cells in Gα13-deficient embryos is sufficient to rescue the endoderm convergence defect and cardia bifida, and, conversely, that the presence of anterior endodermal cells defective for S1pr2 or Gα13 in wild-type embryos causes such defects. Thus, S1pr2/Gα13 signaling probably acts in the endoderm to regulate myocardial migration. In support of this notion, cardiac-specific expression of Gα13 fails to rescue cardia bifida in the context of global Gα13 inhibition. Our data demonstrate for the first time that the Gα13/RhoGEF-dependent pathway functions downstream of S1pr2 to regulate convergent movement of the endoderm, an event that is crucial for coordinating myocardial migration.

Genes / Markers
Figures
Figure Gallery (14 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ha01TgTransgenic Insertion
    m93
      Point Mutation
      twu34TgTransgenic Insertion
        ui1TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          gna12aMO1-gna12aMRPHLNO
          gna13aMO1-gna13aMRPHLNO
          gna13bMO1-gna13bMRPHLNO
          s1pr2MO1-s1pr2MRPHLNO
          1 - 4 of 4
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          Fish
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          1 - 1 of 1
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          Mapping
          No data available