Journal
GASTROENTEROLOGY
Volume 140, Issue 4, Pages 1219-+Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2011.01.033
Keywords
GATA4; GATA6; Crypt Cell Proliferation; Intestinal Differentiation
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Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [RO3-DK-84167, RO1-DK-055743, RO1-DK-066226, RO1-DK-054111, RO1-DK-061382]
- Harvard Digestive Disease Center [5P30-DK-34854]
- National Cancer Institute [RO1-CA-142826]
- Nutricia Research Foundation
- Foundation De Drie Lichten
- Foundation Doctor Catharine van Tussenbroek in The Netherlands.
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BACKGROUND & AIMS: GATA transcription factors regulate proliferation, differentiation, and gene expression in multiple organs. GATA4 is expressed in the proximal 85% of the small intestine and regulates the jejunal-ileal gradient in absorptive enterocyte gene expression. GATA6 is co-expressed with GATA4 but also is expressed in the ileum; its function in the mature small intestine is unknown. METHODS: We investigated the function of GATA6 in small intestine using adult mice with conditional, inducible deletion of Gata6, or Gata6 and Gata4, specifically in the intestine. RESULTS: In ileum, deletion of Gata6 caused a decrease in crypt cell proliferation and numbers of enteroendocrine and Paneth cells, an increase in numbers of goblet-like cells in crypts, and altered expression of genes specific to absorptive enterocytes. In contrast to ileum, deletion of Gata6 caused an increase in numbers of Paneth cells in jejunum and ileum. Deletion of Gata6 and Gata4 resulted in a jejunal and duodenal phenotype that was nearly identical to that in the ileum after deletion of Gata6 alone, revealing common functions for GATA6 and GATA4. CONCLUSIONS: GATA transcription factors are required for crypt cell proliferation, secretory cell differentiation, and absorptive enterocyte gene expression in the small intestinal epithelium.
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