EMT in Normal Development

EMT is a transcriptional reprogramming process whereby epithelial cells change by expressing proteins and morphological features that are normally associated with mesenchymal, fibroblastic cells. Epithelial cells are normally characterized by a cuboidal morphology, a maintenance of cell polarity, where tightly interacting cells interact with each other through homeotypic adhesion processes mediated by cell-cell junction proteins. At the cellular level, epithelial cells undergoing normal EMT can exhibit dramatic changes in morphology and behavior becoming mesenchymal-like in phenotype. Relative to epithelial cells, mesenchymal cells are characterized by their loss of cell polarity and lack of homotypic adhesion, resulting in a spindle-shaped morphology and increased motility and invasiveness, respectively. At the molecular level, EMT transcriptional reprogramming occurs through transcription factors such as Zeb1/TCF8, Snail, Zeb2, Slug, E12/E47 FOXC2, and Twist, and the subsequent activation of factor-specific but overlapping EMT signal-transduction pathways. Important mediators of EMT are integral components in cell survival and proliferation (e.g., transforming growth factor beta [TGFb]; hepatocyte growth factor [HGF]; TGFa; IGF-1) pathways.


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