Snail1, Snail2, and E47 promote mammary epithelial branching morphogenesis

EMBO J. 2011 May 24;30(13):2662-74. doi: 10.1038/emboj.2011.159.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cells, Cultured
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / physiology
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Gene Knockdown Techniques
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / growth & development*
  • Mammary Glands, Animal / metabolism
  • Mice
  • Models, Biological
  • Morphogenesis / drug effects
  • Morphogenesis / genetics*
  • RNA, Small Interfering / pharmacology
  • Snail Family Transcription Factors
  • Transcription Factor 3 / antagonists & inhibitors
  • Transcription Factor 3 / genetics
  • Transcription Factor 3 / metabolism
  • Transcription Factor 3 / physiology*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*


  • RNA, Small Interfering
  • Snai1 protein, mouse
  • Snail Family Transcription Factors
  • Transcription Factor 3
  • Transcription Factors