Whereas the adult gastrointestinal epithelium undergoes tremendous self-renewal 
through active proliferation in crypt stem cell compartments, the responsible 
growth factors regulating this continuous proliferation have not been defined. 
The exploration of physiologic functions of Wnt proteins in adult organisms has 
been hampered by functional redundancy and the necessity for conditional 
inactivation strategies. Dickkopf-1 (Dkk1) is a potent secreted Wnt antagonist 
that interacts with Wnt coreceptors of the LRP family. To address the 
contribution of Wnt signaling to gastrointestinal epithelial proliferation, 
adenoviral expression of Dkk1 was used to achieve stringent, conditional, and 
reversible Wnt inhibition in adult animals. Adenovirus Dkk1 (Ad Dkk1) treatment 
of adult mice repressed expression of the Wnt target genes CD44 and EphB2 within 
2 days in both small intestine and colon, indicating an extremely broad role for 
Wnt signaling in the maintenance of adult gastrointestinal gene expression. In 
parallel, Ad Dkk1 markedly inhibited proliferation in small intestine and colon, 
accompanied by progressive architectural degeneration with the loss of crypts, 
villi, and glandular structure by 7 days. Whereas decreased Dkk1 expression at 
later time points (>10 days) was followed by crypt and villus regeneration, 
which was consistent with a reversible process, substantial mortality ensued 
from colitis and systemic infection. These results indicate the efficacy of 
systemic expression of secreted Wnt antagonists as a general strategy for 
conditional inactivation of Wnt signaling in adult organisms and illustrate a 
striking reliance on a single growth factor pathway for the maintenance of the 
architecture of the adult small intestine and colon.