SMAD2/3 signaling regulates initiation of mouse Wolffian ducts and proximal differentiation in Müllerian ducts.

Male and female reproductive tracts develop from anterior intermediate mesoderm with similar differentiation processes. The anterior intermediate mesoderm develops into the mesonephros, and the Wolffian duct initiates by epithelialization in the mesonephros. The Müllerian duct invaginates from the coelomic epithelium of the cranial mesonephros for ductal formation and is then regionalized into proximal to caudal female reproductive tracts. In this study, we focused on the epithelialization of the Wolffian duct, initiation of the Müllerian duct, and the regionalization step of the Müllerian ducts as a continuous process. By using intermediate mesodermal cells from mouse pluripotent stem cells, we identified that inhibition of SMAD2/3 signaling might be involved in the differentiation into mesenchymal cells, after which mesonephric cells might be then epithelialized during differentiation of the Wolffian duct. Aggregation of coelomic epithelial cells might be related to initiation of the Müllerian duct. Transcriptomic analysis predicted that consensus sequences of SMAD3/4 were enriched among highly expressed genes in the proximal Müllerian duct. SMAD2/3 signaling to regulate differentiation of the Wolffian duct was continuously activated in the proximal Müllerian duct and was involved in proximal and oviductal regionalization. Therefore, SMAD2/3 signaling may be finely tuned to regulate differentiation from initiation to regionalization steps.

Analysis of lead distribution in avian organs by LA-ICP-MS: Study of experimentally lead-exposed ducks and kites.

Lead poisoning of wild birds by ingestion of lead ammunition occurs worldwide. Histopathological changes in organs of lead-intoxicated birds are widely known, and lead concentration of each organ is measurable using mass spectrometry. However, detailed lead localization at the suborgan level has remained elusive in lead-exposed birds. Here we investigated the detailed lead localization in organs of experimentally lead-exposed ducks and kites by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In both the ducks and kites, lead accumulated diffusely in the liver, renal cortex, and brain. Lead accumulation was restricted to the red pulp in the spleen. With regard to species differences in lead distribution patterns, it is noteworthy that intensive lead accumulation was observed in the arterial walls only in the kites. In addition, the distribution of copper in the brain was altered in the lead-exposed ducks. Thus, the present study shows suborgan lead distribution in lead-exposed birds and its differences between avian species for the first time. These findings will provide fundamental information to understand the cellular processes of lead poisoning and the mechanisms of species differences in susceptibility to lead exposure.

The latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus induces expression of the putative oncogene Bcl-3 through activation of the nuclear factor-kappaB.

The Epstein-Barr virus (EBV)-encoded oncoprotein latent membrane protein 1 (LMP1) has an essential role in B-lymphocyte transformation by the virus and is expressed in certain EBV-associated tumors and lymphoproliferative disorders. By using the Flp-In/TREx-inducible expression system, we introduced LMP1 into two human cell lines, Jurkat and HEK-293, and found that in both of them the putative cellular oncogene Bcl-3 is rapidly induced following the expression of LMP1. Bcl-3 was also induced in Ramos cells after in vitro EBV infection and after transfection with an LMP1 expression vector. This LMP1-induced Bcl-3 expression is considered to be mediated by the transcription factor NF-kappaB, because (1) deletion of a critical NF-kappaB-binding site in the Bcl-3 promoter abolished its responsiveness to LMP1, (2) an IkappaB mutant that specifically inhibits NF-kappaB activity suppressed the LMP1-induced activation of the Bcl-3 promoter, and (3) an LMP1 mutant lacking its effector domain CTAR2, required for the activation of NF-kappaB, is severely impaired in its ability to induce Bcl-3. Western blot analyses showed that all EBV-infected and LMP1-expressing lymphoid cell lines express Bcl-3. These results suggest the possibility that Bcl-3 is involved in the pathogenesis of certain EBV-associated malignancies and lymphoproliferative disorders.