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Snail1, Snail2, and E47 promote mammary epithelial branching morphogenesis
Author(s) -
Lee KangAe,
Gjorevski Nikolce,
Boghaert Eline,
Radisky Derek C,
Nelson Celeste M
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.159
Subject(s) - biology , morphogenesis , microbiology and biotechnology , branching (polymer chemistry) , genetics , gene , materials science , composite material
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.