Mesenchymal factor bone morphogenetic protein 4 restricts ductal budding and branching morphogenesis in the developing prostate

The budding of the urogenital sinus epithelium into the surrounding mesench yme signals the onset of prostate morphogenesis. The epithelial and mesench ymal factors that regulate ductal budding and the ensuing process of ductal growth and branching are not fully known. We provide evidence that bone mo rphogenetic protein 4 (BMP4) is a mesenchymal factor that regulates ductal morphogenesis. The Bmp4 gene was most highly expressed in the male urogenit al sinus from embryonic day 14 through birth, a period marked by formation of main prostatic ducts and initiation of ductal branching. from an initial wide distribution throughout the prostatic anlage of the urogenital sinus, Bmp4 expression became progressively restricted to the mesenchyme immediat ely surrounding the nascent prostatic ducts and branches. Exogenous BMP4 in hibited epithelial cell proliferation and exhibited a dose-dependent inhibi tion of ductal budding in urogenital sinus tissues cultured in vitro. Adult Bmp4 haploinsufficient mice exhibited an increased number of duct tips in both the ventral prostate and coagulating gland. Taken together, our data i ndicate that BMP4 is a urogenital sinus mesenchymal factor that restricts p rostate ductal budding and branching morphogenesis. (C) 2001 Academic Press .