This Article Full Text (PDF) Other Versions of this Article: MCB.00124-06v1 26/23/9060    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bosse, T. Articles by Krasinski, S. D. Search for Related Content PubMed PubMed Citation Articles by Bosse, T. Articles by Krasinski, S. D.

 Previous Article  |  Next Article 

Mol. Cell. Biol. doi:10.1128/MCB.00124-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Gata4 is essential for the maintenance of jejunal-ileal identities in the adult mouse small intestine

Department of Medicine, University of Amsterdam, Amsterdam, The Netherlands 1100DD; and Departments of Medicine and Cardiology, Childrens Hospital and Harvard Medical School, Boston, Massachusetts, 02115; and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, 02111

^* To whom correspondence should be addressed. Email: stephen.krasinski{at}childrens.harvard.edu.

	Abstract

Gata4, a member of the zinc finger family of GATA transcription factors, is highly expressed in duodenum and jejunum, but is undetectable in distal ileum of adult mice. We show here that the caudal reduction of Gata4 is conserved in humans. To test the hypothesis that the regional expression of Gata4 is critical for the maintenance of jejunal-ileal homeostasis in the adult small intestine in vivo, we established an inducible, intestine-specific model that results in the synthesis of a transcriptionally inactive Gata4 mutant. Synthesis of mutant Gata4 in jejunum of 6-8 week old mice resulted in an attenuation of absorptive enterocyte genes normally expressed in jejunum but not in ileum, including the anticipated targets liver fatty acid binding protein (Fabp1) and lactase-phlorizin hydrolase (LPH), and a surprising induction of genes normally silent in jejunum but highly expressed in ileum, specifically those involved in bile acid transport. Inactivation of Gata4 resulted in an increase in the goblet cell population, and a redistribution of the enteroendocrine subpopulations, all toward an ileal phenotype. The gene encoding Math1, a known activator of the secretory cell fate, was induced 75% (P<0.05). Gata4 is thus an important positional signal required for the maintenance of jejunal-ileal identities in the adult mouse small intestine.

This article has been cited by other articles:

• Leonie Los, E., Wolters, H., Stellaard, F., Kuipers, F., Verkade, H. J., Rings, E. H. H. M. (2007). Intestinal capacity to digest and absorb carbohydrates is maintained in a rat model of cholestasis. Am. J. Physiol. Gastrointest. Liver Physiol. 293: G615-G622 [Abstract] [Full Text]  
• Belaguli, N. S., Zhang, M., Rigi, M., Aftab, M., Berger, D. H. (2007). Cooperation between GATA4 and TGF-beta signaling regulates intestinal epithelial gene expression. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G1520-G1533 [Abstract] [Full Text]  
• Bosse, T., Fialkovich, J. J., Piaseckyj, C. M., Beuling, E., Broekman, H., Grand, R. J., Montgomery, R. K., Krasinski, S. D. (2007). Gata4 and Hnf1{alpha} are partially required for the expression of specific intestinal genes during development. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G1302-G1314 [Abstract] [Full Text]