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LETTER
doi:10.1038/nature09851
Hedgehog/Wnt feedback supports regenerative
proliferation of epithelial stem cells in bladder
1 1 2 1 1 1 3 1
Kunyoo Shin , John Lee , Nini Guo , James Kim , Agnes Lim , Lishu Qu , Indira U. Mysorekar Philip A. Beachy
Epithelial integrity in metazoan organs is maintained through the Shh is expressed in and has a role in development of urogenital sinus
regulated proliferation and differentiation of organ-specific stem derivatives, including bladder and prostate9–11. In the adult urothelium,
and progenitor cells. Although the epithelia of organs such as the we found that Shh is expressed primarily in Ck5-positive basal cells, as
intestine regenerate constantly and thus remain continuously pro- indicated by immunostaining and GFP expression in a Shh-GFP BAC
liferative1, other organs, such as the mammalian urinary bladder, transgenic strain (Fig. 1d and Supplementary Fig. 5a). Hedgehog (Hh)
shift from near-quiescence to a highly proliferative state in res- pathway activity, indicated by a reporter Gli1-LacZ strain12 (Sup-
ponse to epithelial injury2–4. The cellular and molecular mechan- plementary Fig. 6a, b), is restricted to stromal, submucosal and muscle
isms underlying this injury-induced mode of regenerative response layers, outside the urothelium (Fig. 1e), and depends on the Shh signal,
are poorly defined. Here we show in mice that the proliferative
response to bacterial infection or chemical injury within the bladder
is regulated by signal f
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