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Vol. 18, Issue 11, 4261-4278, November 2007

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Transcriptional Modulation of Genes Encoding Structural Characteristics of Differentiating Enterocytes During Development of a Polarized Epithelium In Vitro

Jennifer M. Halbleib^*,, Annika M. Sääf^,, Patrick O. Brown^,, and W. James Nelson^*,||

Departments of *Molecular and Cellular Physiology, Biochemistry, and ^||Biological Sciences and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305

Submitted April 5, 2007; Revised July 26, 2007; Accepted August 8, 2007
Monitoring Editor: Sandra Schmid

Although there is considerable evidence implicating posttranslational mechanisms in the development of epithelial cell polarity, little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized the temporal program of gene expression during cell–cell adhesion–initiated polarization of human Caco-2 cells in tissue culture, which develop structural and functional polarity similar to that of enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell–cell contacts between neighboring cells. Expression of genes involved in cell proliferation was down-regulated concomitant with induction of genes necessary for functional specialization of polarized epithelial cells. Transcriptional up-regulation of these latter genes correlated with formation of important structural and functional features in enterocyte differentiation and establishment of structural and functional cell polarity; components of the apical microvilli were induced as the brush border formed during polarization; as barrier function was established, expression of tight junction transmembrane proteins peaked; transcripts encoding components of the apical, but not the basal-lateral trafficking machinery were increased during polarization. Coordinated expression of genes encoding components of functional cell structures were often observed indicating temporal control of expression and assembly of multiprotein complexes.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

These authors contributed equally to this work.

Address correspondence to: W. James Nelson (wjnelson{at}stanford.edu) or Patrick O. Brown (pbrown{at}cmgm.stanford.edu).