Abstract
Wnt signaling is a key regulator of intestinal epithelial homeostasis. Since the large intestine exhibits considerable morphological and functional heterogeneity along its length, we investigated whether this can be explained by local differences in Wnt signaling. Furthermore, we examined whether divergent Wnt signaling may be shaped by commensal bacteria. Using a Wnt PCR array, expression of 84 genes related to Wnt‐mediated signal transduction was analyzed. A differential signature of Wnt related genes in the proximal vs. distal murine colon was identified. Specifically, we observed that Wnt agonists Wnt5a, Wnt8b, and Wnt11, Wnt receptors Fzd3 and Lrp6, and a Wnt inhibitory factor Wif1 were differentially expressed along the colon length. These Wnt signatures were associated with differential epithelial cell proliferation and migration in the proximal vs. distal colon. Given the importance of luminal bacteria in controlling epithelial homeostasis, Wnt gene expression in colonic segments of mice raised in germ‐free conditions were analyzed. Altered expression of Wnt genes was identified in mice raised in germ‐free vs. specific pathogen free conditions. These results suggest that the morphological and physiological heterogeneity within the colon is in part facilitated by differential expression of Wnt signaling components and influenced by colonization with bacteria.
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