Specific GATA factors act as conserved inducers of an endodermal-EMT

Dev Cell. 2011 Dec 13;21(6):1051-61. doi: 10.1016/j.devcel.2011.10.005.

Abstract

The epithelial-to-mesenchymal transition (EMT) converts cells from static epithelial to migratory mesenchymal states (Hay, 1995). Here, we demonstrate that EMT in the Drosophila endoderm is dependent on the GATA-factor Serpent (Srp), and that Srp acts as a potent trigger for this transition when activated ectopically. We show that Srp affects endodermal-EMT through a downregulation of junctional dE-Cadherin (dE-Cad) protein, without a block in its transcription. Moreover, the relocalization of dE-Cad is achieved through the direct repression of crumbs (crb) by Srp. Finally, we show that hGATA-6, an ortholog of Srp, induces a similar transition in mammalian cells. Similar to Srp, hGATA-6 acts through the downregulation of junctional E-Cad, without blocking its transcription, and induces the repression of a Crumbs ortholog, crb2. Together, these results identify a set of GATA factors as a conserved alternative trigger to repress epithelial characteristics and confer migratory capabilities on epithelial cells in development and pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line
  • Cell Polarity
  • Dogs
  • Down-Regulation
  • Drosophila / cytology
  • Drosophila / embryology*
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Endoderm / cytology
  • Endoderm / embryology*
  • Endoderm / metabolism*
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / physiology
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism*
  • GATA4 Transcription Factor / genetics
  • GATA4 Transcription Factor / metabolism
  • GATA6 Transcription Factor / genetics
  • GATA6 Transcription Factor / metabolism
  • Gastrointestinal Tract / cytology
  • Gastrointestinal Tract / embryology
  • Gastrointestinal Tract / metabolism
  • Gene Expression Regulation, Developmental
  • Genes, Insect
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mutation
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Cadherins
  • Drosophila Proteins
  • GATA Transcription Factors
  • GATA4 Transcription Factor
  • GATA4 protein, human
  • GATA6 Transcription Factor
  • GATA6 protein, human
  • Membrane Proteins
  • Recombinant Proteins
  • crb protein, Drosophila
  • shg protein, Drosophila
  • srp protein, Drosophila