Role For Ilk In The Control Of Fibronectin Expression And Deposition In Human Intestinal Epithelial Cells

may signify intestinalization of a previously undetermined gut endoderm.To investigate whether other changes in gene expression accompany this event, we used oligonucleotide microarrays to explore global patterns of gene expression across the forming pyloric border at E14.5 and E16.5.The data reveal that, at E14.5, the duodenum and antrum are remarkably similar in gene expression.By E16.5 however, the duodenum develops a distinct gene expression pattern, while the stomach remains largely unchanged.Furthermore, based on previously published microarray data, we know that most of these changes are occurring in the epithelium.These data highlight an intriguing possibility: that a program of gene activation occurs at E16.5 only in the intestinal domain, and that this activation program is repressed specifically in the stomach. To begin to probe the molecular basis of endoderm intestinalization, we examined the expression of epithelial transcription factors and identified several that were upregulated in E16.5 duodenum.Interestingly, sixteen of the seventeen most highly expressed were represented by just four families of transcription factors: basic leucine zipper (bZip), helix-loop-helix (HLH), homeobox (Hox), and nuclear hormone receptor (NHR).Furthermore, no bZip or NHR transcription factors were observed in the top eight mesenchymal hits, suggesting that these families may regulate sets of genes with a particular function critical for the specification of intestinal epithelial cell identity.Tcfec, a bHLH-Zip transcription factor, and Hnf4γ, a member of the NHR family, are among the most significantly upregulated transcription factors in duodenal epithelium at E16.5, and thus present themselves as intriguing targets for further study.Continued investigation of this dramatic developmental intestinalization process may hold promise for understanding the mechanisms underlying the formation of intestinal metaplasia in the adult.