During prostate gland organogenesis the fetal urogenital sinus mesenchyme induces and directs the phenotypic differentiation of the apposing epithelium. This leads to the formation of glandular ducts and acini, typical of the adult gland morphology. Previous studies from Dr. Rowley's laboratory have used organ cultures of fetal urogenital sinus to identify potential growth and differentiation regulatory factors from mesenchyme. These studies have identified a growth inhibitory factor in the conditioned medium from urogenital sinus organ cultures and derived mesenchymal cell lines. In addition, the growth inhibitory activity affects bladder and prostatic epithelial cell lines, suggesting this activity may affect cell differentiation. The protein responsible for activity has been purified to near homogeneity. The long term goals of this project are to understand the fundamental role of this factor, termed UGIF, in mesenchymal epithelial interactions during organogenesis. The immediate objectives of the studies proposed here are: to develop antibody and oligonucleotide probes specific for the UGIF protein; to isolate and clone the cDNA encoding UGIF and; to determine the spatial and temporal pattern of expression of UGIF in vivo. The proposed studies will set the foundation to determine the potential significance of UGIF as a regulatory factor in vivo, and its specific role in the basic mechanisms of mesenchymal epithelial interactions and associated organogenesis.
