Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium. (10th March 2015)

• Record Type: Journal Article
• Authors: Horvay, Katja; Jardé, Thierry; Casagranda, Franca; Perreau, Victoria M; Haigh, Katharina; Nefzger, Christian M; Akhtar, Reyhan; Gridley, Thomas; Berx, Geert; Haigh, Jody J; Barker, Nick; Polo, Jose M; Hime, Gary R; Abud, Helen E
• Is Part Of: EMBO journal. Volume 34:Number 10(2015)
• Page Start: 1319
• Page End: 1335
• Publication Date: 2015-03-10
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201490881
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main" id="embj201490881-abs-0001"> <title>Abstract</title> <p>Snail family members regulate epithelial‐to‐mesenchymal transition (EMT) during invasion of intestinal tumours, but their role in normal intestinal homeostasis is unknown. Studies in breast and skin epithelia indicate that Snail proteins promote an undifferentiated state. Here, we demonstrate that conditional knockout of <italic>Snai1</italic> in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells and bias towards differentiation of secretory lineages. <italic>In vitro</italic> organoid cultures derived from <italic>Snai1</italic> conditional knockout mice also undergo apoptosis when <italic>Snai1</italic> is deleted. Conversely, ectopic expression of <italic>Snai1</italic> in the intestinal epithelium <italic>in vivo</italic> results in the expansion of the crypt base columnar cell pool and a decrease in secretory enteroendocrine and Paneth cells. Following conditional deletion of <italic>Snai1</italic>, the intestinal epithelium fails to produce a proliferative response following radiation‐induced damage indicating a fundamental requirement for <italic>Snai1</italic> in epithelial regeneration. These results demonstrate that <italic>Snai1</italic> is required for regulation of lineage choice, maintenance of CBC stem cells and regeneration of the intestinal epithelium following damage.</p> </abstract>