PUBLICATION

Gbeta1 controls collective cell migration by regulating the protrusive activity of leader cells in the posterior lateral line primordium

Authors
Xu, H., Ye, D., Behra, M., Burgess, S., Chen, S., and Lin, F.
ID
ZDB-PUB-131204-3
Date
2014
Source
Developmental Biology   385(2): 316-27 (Journal)
Registered Authors
Behra, Martine, Burgess, Shawn, Lin, Fang, Xu, Hui, Ye, Ding
Keywords
zebrafish, G protein, Gβ1, posterior lateral line primordium, cell migration
MeSH Terms
  • Chemokine CXCL12/metabolism
  • Lateral Line System/cytology
  • Lateral Line System/metabolism*
  • In Situ Hybridization
  • Signal Transduction
  • Receptors, CXCR4/metabolism
  • DNA Primers
  • Heterotrimeric GTP-Binding Proteins/metabolism
  • Heterotrimeric GTP-Binding Proteins/physiology*
  • Cell Movement/physiology*
  • Zebrafish
  • Base Sequence
  • Animals
  • In Situ Nick-End Labeling
  • Zebrafish Proteins/metabolism
  • Animals, Genetically Modified
(all 16)
PubMed
24201188 Full text @ Dev. Biol.
Abstract

Collective cell migration is critical for normal development, tissue repair and cancer metastasis. Migration of the posterior lateral line primordium (pLLP) generates the zebrafish sensory organs (neuromasts, NMs). This migration is promoted by the leader cells at the leading edge of the pLLP, which express the G protein-coupled chemokine receptor Cxcr4b and respond to the chemokine Cxcl12a. However, the mechanism by which Cxc112a/Cxcr4b signaling regulates pLLP migration remains unclear. Here we report that signal transduction by the heterotrimeric G protein subunit Gβ1 is essential for proper pLLP migration. Although both Gβ1 and Gβ4 are expressed in the pLLP and NMs, depletion of Gβ1 but not Gβ4 resulted in an arrest of pLLP migration. In embryos deficient for Gβ1, the pLLP cells migrated in an uncoordinated fashion and were unable to extend protrusions at the leading front, phenocopying those in embryos deficient for Cxcl12a or Cxcr4b. A transplantation assay showed that, like Cxcr4b, Gβ1 is required only in the leader cells of the pLLP. Analysis of F-actin dynamics in the pLLP revealed that whereas wild-type leader cells display extensive actin polymerization in the direction of pLLP migration, counterparts defective for Gβ1, Cxcr4b or Cxcl12a do not. Finally, synergy experiments revealed that Gβ1 and Cxcr4b interact genetically in regulating pLLP migration. Collectively, our data indicate that Gβ1 controls migration of the pLLP, likely by acting downstream of the Cxcl12a/Cxcr4b signaling. This study also provides compelling evidence for functional specificity among Gβ isoforms in vivo.

Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
cxcr4bt26035/+; zf106Tg + MO2-gnb1a + MO2-gnb1b + MO4-tp53standard conditionsLong-pec
cxcr4bt26035/+; zf106Tg + MO2-gnb1a + MO2-gnb1b + MO4-tp53standard conditionsLong-pec
ui2Tg; zf106Tg + MO2-cxcl12a + MO4-tp53standard conditionsPrim-15
ui2Tg; zf106Tg + MO2-gnb1a + MO2-gnb1b + MO4-tp53standard conditionsPrim-15
ui2Tg; zf106Tg + MO4-tp53 + MO7-cxcr4bstandard conditionsPrim-15
zf106Tg + MO1-gnb4a + MO1-gnb4b + MO4-tp53standard conditionsLong-pec
zf106Tg + MO1-gnb4a + MO1-gnb4b + MO4-tp53standard conditionsLong-pec
zf106Tg + MO2-gnb1a + MO2-gnb1b + MO4-tp53standard conditionsPrim-5 to Prim-25
zf106Tg + MO2-gnb1a + MO2-gnb1b + MO4-tp53standard conditionsPrim-5 to Prim-25
zf106Tg + MO2-gnb1a + MO2-gnb1b + MO4-tp53standard conditionsPrim-15
1 - 10 of 21
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
sqet20EtTransgenic Insertion
    t26035
      Point Mutation
      ui2TgTransgenic Insertion
        y229GtTransgenic Insertion
        zf106TgTransgenic Insertion
          1 - 5 of 5
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          cxcl12aMO2-cxcl12aMRPHLNO
          cxcr4bMO7-cxcr4bMRPHLNO
          gnb1aMO1-gnb1aMRPHLNO
          gnb1aMO2-gnb1aMRPHLNO
          gnb1bMO2-gnb1bMRPHLNO
          gnb1bMO3-gnb1bMRPHLNO
          gnb4aMO1-gnb4aMRPHLNO
          gnb4aMO2-gnb4aMRPHLNO
          gnb4bMO1-gnb4bMRPHLNO
          gnb4bMO2-gnb4bMRPHLNO
          1 - 10 of 11
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          Fish
          Antibodies
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          RFPEFGRFP
          1 - 2 of 2
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          Mapping
          No data available