title: Specific GATA factors act as conserved inducers of an endodermal-EMT.
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.
authors.affiliation: Institut de Biologia Molecular de Barcelona-CSIC, Parc Cientific de Barcelona, 08028 Barcelona, Spain.
authors.forename: Kyra
authors.initials: K
authors.lastname: Campbell
authors.forename: Gavin
authors.initials: G
authors.lastname: Whissell
authors.forename: Xavier
authors.initials: X
authors.lastname: Franch-Marro
authors.forename: Eduard
authors.initials: E
authors.lastname: Batlle
authors.forename: Jordi
authors.initials: J
authors.lastname: Casanova
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D015536:Down-Regulation; D004330:Drosophila / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050993:GATA6 Transcription Factor / Q000235:genetics / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; D050980:GATA Transcription Factors; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; D008565:Membrane Proteins; D011994:Recombinant Proteins; C064360:crb protein, Drosophila; C501889:shg protein, Drosophila; C103965:srp protein, Drosophila