Snail1, Snail2, and E47 promote mammary epithelial branching morphogenesis

Kangae Lee, Nikolce Gjorevski, Eline Boghaert, Derek C. Radisky, Celeste M. Nelson

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Several E-box-binding transcription factors regulate individual and collective cell migration and enhance the motility of epithelial cells by promoting epithelial-mesenchymal transition (EMT). Here, we characterized the role of a subset of these transcription factors and the EMT proteome in branching morphogenesis of mammary epithelial tissues using a three-dimensional organotypic culture model of the mammary duct. We found that the transcription factors Snail1, Snail2, and E47 were transiently upregulated at branch sites; decreasing the expression of these transcription factors inhibited branching. Conversely, ectopic expression of Snail1, Snail2, and E47 induced branching in the absence of exogenous stimuli. These changes correlated with the expression of mesenchymal markers and repression of E-cadherin, which was essential for branching. Snail1 and Snail2 also promoted cell survival at branch sites, but this was not sufficient to induce branching. These findings indicate that Snail1, Snail2, and E47 can promote collective migration during branching morphogenesis of mammary epithelial tissues through key regulators of EMT.

Original languageEnglish (US)
Pages (from-to)2662-2674
Number of pages13
JournalEMBO Journal
Volume30
Issue number13
DOIs
StatePublished - Jul 6 2011

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Keywords

  • 3D
  • Slug
  • engineered tissue
  • mechanical stress
  • patterning

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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