Gata4 is essential for the maintenance of Jejunal-Ileal identities in the adult mouse small intestine

被引:105
作者
Bosse, Tjalling
Piaseckyj, Christina M.
Burghard, Ellen
Fialkovich, John J.
Rajagopal, Satish
Pu, William T.
Krasinski, Stephen D.
机构
[1] Childrens Hosp, EN 720, Dept Med, Boston, MA 02115 USA
[2] Childrens Hosp, EN 720, Dept Cardiol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Boston, MA 02115 USA
[4] Univ Amsterdam, Dept Med, NL-1100 DD Amsterdam, Netherlands
[5] Tufts Univ, Dorothy R Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA
关键词
D O I
10.1128/MCB.00124-06
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 similar to 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.
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页码:9060 / 9070
页数:11
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