title: Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium.
abstract: 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 Snai1 in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snai1 conditional knockout mice also undergo apoptosis when Snai1 is deleted. Conversely, ectopic expression of Snai1 in the intestinal epithelium in vivo results in the expansion of the crypt base columnar cell pool and a decrease in secretory enteroendocrine and Paneth cells. Following conditional deletion of Snai1, the intestinal epithelium fails to produce a proliferative response following radiation-induced damage indicating a fundamental requirement for Snai1 in epithelial regeneration. These results demonstrate that Snai1 is required for regulation of lineage choice, maintenance of CBC stem cells and regeneration of the intestinal epithelium following damage.
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia.
authors.forename: Katja
authors.initials: K
authors.lastname: Horvay
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia.
authors.forename: Thierry
authors.initials: T
authors.lastname: Jardé
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Vic., Australia.
authors.forename: Franca
authors.initials: F
authors.lastname: Casagranda
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Vic., Australia.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Perreau
authors.affiliation: Australian Centre for Blood Diseases, Monash University & Alfred Health, Melbourne, Vic., Australia Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Katharina
authors.initials: K
authors.lastname: Haigh
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia Australian Regenerative Medicine Institute, Monash University, Clayton, Vic., Australia.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Nefzger
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia.
authors.forename: Reyhan
authors.initials: R
authors.lastname: Akhtar
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gridley
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium Molecular and Cellular Oncology, Inflammation Research Center, VIB, Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Berx
authors.affiliation: Australian Centre for Blood Diseases, Monash University & Alfred Health, Melbourne, Vic., Australia Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Jody J
authors.initials: JJ
authors.lastname: Haigh
authors.affiliation: A*STAR Institute of Medical Biology, Singapore City, Singapore.
authors.forename: Nick
authors.initials: N
authors.lastname: Barker
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia Australian Regenerative Medicine Institute, Monash University, Clayton, Vic., Australia.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Polo
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Vic., Australia g.hime@unimelb.edu.au helen.abud@monash.edu.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hime
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia g.hime@unimelb.edu.au helen.abud@monash.edu.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Abud
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; C470380:Serinc3 protein, mouse; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
keywords: SerinC3; Snail; apoptosis; intestinal stem cell; organoid