PUBLICATION

Stat3/Cdc25a-dependent cell proliferation promotes embryonic axis extension during zebrafish gastrulation

Authors
Liu, Y., Sepich, D.S., Solnica-Krezel, L.
ID
ZDB-PUB-170222-3
Date
2017
Source
PLoS Genetics   13: e1006564 (Journal)
Registered Authors
Liu, Yinzi, Sepich, Diane, Solnica-Krezel, Lilianna
Keywords
Embryos, Cell cycle and cell division, Zebrafish, Cell proliferation, Notochords, Phenotypes, Embryogenesis, STAT signaling
MeSH Terms
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics*
  • Mutant Proteins/genetics
  • Morphogenesis/genetics
  • Humans
  • Cell Proliferation/genetics*
  • Gene Expression Regulation, Developmental
  • Gastrulation/genetics
  • Embryonic Development/genetics*
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • STAT3 Transcription Factor/biosynthesis
  • STAT3 Transcription Factor/genetics*
  • cdc25 Phosphatases/biosynthesis
  • cdc25 Phosphatases/genetics*
  • Animals
  • Cell Polarity/genetics
  • Gastrula/growth & development
(all 18)
PubMed
28222105 Full text @ PLoS Genet.
Abstract
Cell proliferation has generally been considered dispensable for anteroposterior extension of embryonic axis during vertebrate gastrulation. Signal transducer and activator of transcription 3 (Stat3), a conserved controller of cell proliferation, survival and regeneration, is associated with human scoliosis, cancer and Hyper IgE Syndrome. Zebrafish Stat3 was proposed to govern convergence and extension gastrulation movements in part by promoting Wnt/Planar Cell Polarity (PCP) signaling, a conserved regulator of mediolaterally polarized cell behaviors. Here, using zebrafish stat3 null mutants and pharmacological tools, we demonstrate that cell proliferation contributes to anteroposterior embryonic axis extension. Zebrafish embryos lacking maternal and zygotic Stat3 expression exhibit normal convergence movements and planar cell polarity signaling, but transient axis elongation defect due to insufficient number of cells resulting largely from reduced cell proliferation and increased apoptosis. Pharmacologic inhibition of cell proliferation during gastrulation phenocopied axis elongation defects. Stat3 regulates cell proliferation and axis extension in part via upregulation of Cdc25a expression during oogenesis. Accordingly, restoring Cdc25a expression in stat3 mutants partially suppressed cell proliferation and gastrulation defects. During later development, stat3 mutant zebrafish exhibit stunted growth, scoliosis, excessive inflammation, and fail to thrive, affording a genetic tool to study Stat3 function in vertebrate development, regeneration, and disease.
Genes / Markers
Figures
Figure Gallery (16 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
sa15744
    Point Mutation
    stl27
      Small Deletion
      stl28
        Indel
        tz216
          Point Mutation
          vu67
            Point Mutation
            1 - 5 of 5
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            stat3MO1-stat3MRPHLNO
            stat3TALEN1-stat3TALEN
            1 - 2 of 2
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            Fish
            Antibodies
            Orthology
            No data available
            Engineered Foreign Genes
            No data available
            Mapping
            No data available