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Molecular and Cellular Biology, December 2006, p. 9060-9070, Vol. 26, No. 23
0270-7306/06/$08.00+0     doi:10.1128/MCB.00124-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Gata4 Is Essential for the Maintenance of Jejunal-Ileal Identities in the Adult Mouse Small Intestine{triangledown}

Tjalling Bosse,1 Christina M. Piaseckyj,2 Ellen Burghard,1 John J. Fialkovich,2 Satish Rajagopal,3 William T. Pu,3 and Stephen D. Krasinski2,4*

Department of Medicine, University of Amsterdam, Amsterdam 1100DD, The Netherlands; Departments of,1 Medicine,2 Cardiology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115,3 Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts 021114

Received 20 January 2006/ Returned for modification 17 March 2006/ Accepted 22 August 2006

Gata4, a member of the zinc finger family of GATA transcription factors, is highly expressed in duodenum and jejunum but is nearly 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 jejuna of 6- to 8-week-old mice resulted in an attenuation of absorptive enterocyte genes normally expressed in jejunum but not in ileum, including those for 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.

* Corresponding author. Mailing address: GI/Cell Biology, EN 720, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115. Phone: (617) 919-2136. Fax: (617) 730-0498. E-mail: stephen.krasinski{at}childrens.harvard.edu.

{triangledown} Published ahead of print on 28 August 2006.

Molecular and Cellular Biology, December 2006, p. 9060-9070, Vol. 26, No. 23
0270-7306/06/$08.00+0     doi:10.1128/MCB.00124-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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