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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/G1302    most recent 00418.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) 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.

MUCOSAL BIOLOGY

Gata4 and Hnf1 are partially required for the expression of specific intestinal genes during development

¹School of Medicine, University of Amsterdam, Amsterdam, The Netherlands; ²Division of Gastroenterology and Nutrition, Department of Medicine, Children's Hospital Boston, Boston, Massachusetts; ³School of Medicine, Erasmus University Rotterdam, Rotterdam, The Netherlands; ⁴School of Medicine, University of Utrecht, Utrecht, The Netherlands; ⁵Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; and ⁶Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts

Submitted 9 September 2006 ; accepted in final form 25 January 2007

The terminal differentiation phases of intestinal development in mice occur during cytodifferentiation and the weaning transition. Lactase-phlorizin hydrolase (LPH), liver fatty acid binding protein (Fabp1), and sucrase-isomaltase (SI) are well-characterized markers of these transitions. With the use of gene inactivation models in mature mouse jejunum, we have previously shown that a member of the zinc finger transcription factor family (Gata4) and hepatocyte nuclear factor-1 (Hnf1) are each indispensable for LPH and Fabp1 gene expression but are both dispensable for SI gene expression. In the present study, we used these models to test the hypothesis that Gata4 and Hnf1 regulate LPH, Fabp1, and SI gene expression during development, specifically focusing on cytodifferentiation and the weaning transition. Inactivation of Gata4 had no effect on LPH gene expression during either cytodifferentiation or suckling, whereas inactivation of Hnf1 resulted in a 50% reduction in LPH gene expression during these same time intervals. Inactivation of Gata4 or Hnf1 had a partial effect (50% reduction) on Fabp1 gene expression during cytodifferentiation and suckling but no effect on SI gene expression at any time during development. Throughout the suckling period, we found a surprising and dramatic reduction in Gata4 and Hnf1 protein in the nuclei of absorptive enterocytes of the jejunum despite high levels of their mRNAs. Finally, we show that neither Gata4 nor Hnf1 mediates the glucocorticoid-induced precocious maturation of the intestine but rather are downstream targets of this process. Together, these data demonstrate that specific intestinal genes have differential requirements for Gata4 and Hnf1 that are dependent on the developmental time frame in which they are expressed.

lactase-phlorizin hydrolase; liver fatty acid binding protein; sucrase-isomaltase; intestinal differentiation; cytodifferentiation; weaning