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?6C, G, and H). We found that loss of Notch/RBP-J function resulted in a significant decrease in cell survival in the UGS epithelium. Specifically, Nkx3.1Cre/+;RBP-Jflox/flox P1 prostates contained 30% (P?click here specification of the prostate lobes. However, we found severe defects in organization of the Nkx3.1Cre/+;RBP-Jflox/flox UGS epithelium ( Fig.?7). Normally, at the embryonic and early postnatal stages, urethral epithelium is multilayered and pseudostratified ( Marker et al., 2003). This was confirmed by histological analysis ( Figs.?7A�CB), and labeling of the wild-type P1 UGS for CK14 ( Figs.?7C and D). In contrast, Nkx3.1Cre/+;RBP-Jflox/flox UGS epithelium consisted of a single layer of cuboidally shaped cells ( Fig.?7H). Nkx3.1Cre/+;RBP-Jflox/flox UGS epithelium also showed significant shedding of cells into the lumen ( Figs.?7E 17-DMAG (Alvespimycin) HCl and F arrowheads) consistent with increased levels of cell death ( Figs.?6G and H). This data indicates that loss of Notch/RBP-J function resulted in significant defects in differentiation and organization of the UGS epithelium. We further determined whether loss of RBP-J affected maintenance of epithelial and smooth muscle progenitors in the postnatal prostate. Immunolabeling for p63 showed that Nkx3.1Cre/+;RBP-Jflox/flox prostates rapidly loose p63+ basal cells postnatally ( Figs.?8A�CE). At P1, Nkx3.1Cre/+;RBP-Jflox/flox prostate ducts showed about 59% (P?I BET151 2008). Thus, the increase in PTEN in the Nkx3.1Cre/+;RBP-Jflox/flox prostate epithelium is likely to account for the decreased survival and proliferation of the p63+ cells. Further examination of Nkx3.1Cre/+;RBP-Jflox/flox periductal stroma at P7 showed significantly lower content of ��-sma+ cells, as well as discontinuous smooth muscle envelopes in the distal regions of the gland ( Figs.?8J compare to I). We also found that within prostate stroma, high levels of PTEN are present only in vimentin+ cells, namely, in vimentin+��-sma? fibrobasts and vimentin+��-sma+ myofibroblasts ( Fig. 9).