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Publication : Differential stage-dependent regulation of prostatic epithelial morphogenesis by Hedgehog signaling.

First Author  Yu M Year  2013
Journal  Dev Biol Volume  380
Issue  1 Pages  87-98
PubMed ID  23660337 Mgi Jnum  J:199591
Mgi Id  MGI:5503261 Doi  10.1016/j.ydbio.2013.04.032
Citation  Yu M, et al. (2013) Differential stage-dependent regulation of prostatic epithelial morphogenesis by Hedgehog signaling. Dev Biol 380(1):87-98
abstractText  Published studies of Hh (Hedgehog) signaling in the developing prostate have reported varying and discrepant effects on epithelial proliferation, ductal morphogenesis and growth. We report here that these differing observations accrue from stage-specific effects of Hh signaling in the developing prostate. Using in vitro organ cultures of the E16 UGS and P1 prostate, we show that ectopic Hh pathway activation stimulates epithelial proliferation prenatally, but inhibits epithelial proliferation postnatally. Extrapolating from previously published observations that Hh target gene expression is altered in the reactive stroma of prostate cancer, we examined and found discordant regulation of a subset of target genes by Hh signaling in the prenatal and postnatal prostate. Cell based studies and recombination assays show that these changes are not simply attributable to the age of the mesenchyme or the epithelium, but more likely reflect a complex regulation by the cellular microenvironment. To determine the in vivo relevance of these observations, we examined the effect of transgenic activation of Hh signaling on epithelial proliferation in the prenatal and postnatal prostate and confirmed the operation of stage-specific effects. These observations demonstrate stage-specific differences in the effect of Hh signaling on epithelial proliferation in the developing prostate and suggest that these are a product of complex interactions determined by the cellular microenvironment.
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