Journal article

Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium

Katja Horvay, Thierry Jarde, Franca Casagranda, Victoria M Perreau, Katharina Haigh, Christian M Nefzger, Reyhan Akhtar, Thomas Gridley, Geert Berx, Jody J Haigh, Nick Barker, Jose M Polo, Gary R Hime, Helen E Abud

EMBO JOURNAL | WILEY | Published : 2015

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..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) Australia


Awarded by EU-FP7 Framework Program


Awarded by NIH


Awarded by EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT


Funding Acknowledgements

We thank staff at Monash Animal Services, Helen Lescesen and Emma Murphy for assistance with genotyping. The authors acknowledge the facilities and scientific and technical assistance of Monash Micro Imaging and Histology platform at Monash University, Victoria, Australia. This work was supported by National Health and Medical Research Council (NH&MRC) Australia, project grant (509158) to H.E.A. and G.R.H. and (1011187) to H.E.A. and N.B. G.B.'s work was funded by grants from VIB, the geconcerteerde onderzoeksacties of Ghent University, the stichting tegen kanker and the EU-FP7 Framework Program TuMIC 2008-201662. T.G. was funded by NIH Grant HD034883.