Regulation of gene expression by Pdx‐1 in the small intestine

Transcription factor pancreatic duodenal homeobox‐1 (Pdx‐1) plays a key role in pancreatic development and maintaining pancreatic islet function. However, the role of Pdx‐1 in intestinal development and gene expression is less well defined. The present study aimed to identify Pdx‐1 target genes in small intestine. Microarray analysis was performed with total RNA isolated from control human intestinal Caco‐2 cells and from Caco‐2 cells stably expressing mouse Pdx‐1. Eighty‐eight genes were activated while 49 genes were repressed (>4‐fold) by Pdx‐1 overexpression. The effect of Pdx‐1 on selected genes was confirmed by real‐time RT‐PCR. Genes that were regulated by Pdx‐1 overexpression include transcription factors, growth factors, kinases, digestive glycosidases, nutrient transporters, nutrient binding proteins, and structural components. To characterize Pdx‐1 regulation of target genes in vivo, conditional knockout (KO) mice with Pdx‐1 inactivation restricted to the intestine were generated. Total RNA isolated from the small intestine segments of control and conditional KO mice was analyzed by real‐time RT‐PCR. The expression of adenosine deaminase (ADA) was reduced significantly in the proximal small intestine of the KO mouse, consistent with the published finding that Pdx‐1 activates ADA. Sucrase‐isomaltase and lactase gene expression was increased in the proximal small intestine of the KO mouse, in agreement with the hypothesis that Pdx‐1 is a repressor for both genes. The Pdx‐1 conditional KO mouse represents a useful tool for investigating Pdx‐1 target genes in vivo in the context of spatial patterning of the gut.