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The rate of migration of epithelial cells as defined by the cumulative frequency of BrdU-positive cells along the crypt�Cvillus axis was also higher in the small intestine of Klf4��IS mice compared to the control littermates at learn more 4?h (p?SWAP70 for cleaved caspase-3 but found no difference in the rate of apoptosis between the two groups (data not shown). These results indicate that both the rates of proliferation and migration along the crypt�Cvillus axis are increased when Klf4 is deleted from the small intestine. The effect of intestinal Klf4 deletion on cellular differentiation was then investigated. Differentiation of intestinal epithelial cells into goblet cells was examined by staining for acidic, neutral, and Muc2 mucins using Alcian blue (AB), Periodic-acid Schiff (PAS), and anti-Muc2 stains, respectively. Compared to the controls, Klf4��IS mice Selleckchem BIBW2992 showed a reduction in acidic mucin expression, as demonstrated by AB staining, in the small intestine but no change in neutral mucin or Muc2 mucin expression ( Fig. 3A�CF). In contrast, the colon of Klf4��IS mice showed an overall altered goblet cell maturation and differentiation as indicated by the reduction in staining for all three mucins ( Fig. 3G�CL), as well as a reduction in the number and size of goblet cells, when compared to the controls ( Suppl. Figs. S2A and B). These results support the previous finding that Klf4 is required for terminal differentiation of goblet cells in the colon of one day-old Klf4-null mice ( Katz et al., 2002). The intestinal alkaline phosphatase (ALP) gene is only expressed in differentiated enterocytes of the small intestine and has been shown to be an in vitro target gene of KLF4 ( Hinnebusch et al., 2004). To investigate the effect of intestinal Klf4 deletion on the terminal differentiation of enterocytes, we stained the small intestine for ALP. Compared to the controls, the small intestine of Klf4��IS mice showed a reduction in ALP staining, indicating altered differentiation of intestinal enterocytes ( Fig. 4A and B). In the colon, the effect of Klf4 deletion on the terminal differentiation of colonocytes was determined by staining for carbonic anhydrase-1 (CA1). CA1 is expressed in the colonic epithelium but not the small intestine ( Parkkila et al., 1994?and?Sowden et al., 1993).