Wwtr1 is a widely expressed 14-3-3-binding protein that regulates the activity of several transcription factors involved in development and disease. To elucidate the physiological role of Wwtr1, we generated Wwtr1 ؊/؊ mice by homologous recombination. Surprisingly, although Wwtr1 is known to regulate the activity of Cbfa1, a transcription factor important for bone development, Wwtr1 ؊/؊ mice show only minor skeletal defects. However, Wwtr1 ؊/؊ animals present with renal cysts that lead to end-stage renal disease. Cysts predominantly originate from the dilation of Bowman's spaces and atrophy of glomerular tufts, reminiscent of glomerulocystic kidney disease in humans. A smaller fraction of cysts is derived from tubules, in particular the collecting duct (CD). The corticomedullary accumulation of cysts also shows similarities with nephronophthisis. Cells lining the cysts carry fewer and shorter cilia and the expression of several genes associated with glomerulocystic kidney disease (Ofd1 and Tsc1) or encoding proteins involved in cilia structure and/or function (Tg737, Kif3a, and Dctn5) is decreased in Wwtr1 ؊/؊ kidneys. The loss of cilia integrity and the down-regulation of Dctn5, Kif3a, Pkhd1 and Ofd1 mRNA expression can be recapitulated in a renal CD epithelial cell line, mIMCD3, by reducing Wwtr1 protein levels using siRNA. Thus, Wwtr1 is critical for the integrity of renal cilia and its absence in mice leads to the development of renal cysts, indicating that Wwtr1 may represent a candidate gene for polycystic kidney disease in humans.bone ͉ cilia ͉ cysts ͉ glomerulus ͉ gene expression

Although it is known that OCT4-NANOG are required for maintenance of pluripotent cells in vitro, the upstream signals that regulate this circuit during early development in vivo have not been identified. Here we demonstrate, for the first time, signal transducers and activators of transcription 3 (STAT3)-dependent regulation of the OCT4-NANOG circuitry necessary to maintain the pluripotent inner cell mass (ICM), the source of in vitro-derived embryonic stem cells (ESCs). We show that STAT3 is highly expressed in mouse oocytes and becomes phosphorylated and translocates to the nucleus in the four-cell and later stage embryos. Using leukemia inhibitory factor (Lif )-null embryos, we found that STAT3 phosphorylation is dependent on LIF in four-cell stage embryos. In blastocysts, interleukin 6 (IL-6) acts in an autocrine fashion to ensure STAT3 phosphorylation, mediated by janus kinase 1 (JAK1), a LIF-and IL-6-dependent kinase. Using genetically engineered mouse strains to eliminate Stat3 in oocytes and embryos, we firmly establish that STAT3 is essential for maintenance of ICM lineages but not for ICM and trophectoderm formation. Indeed, STAT3 directly binds to the Oct4 and Nanog distal enhancers, modulating their expression to maintain pluripotency of mouse embryonic and induced pluripotent stem cells. These results provide a novel genetic model of cell fate determination operating through STAT3 in the preimplantation embryo and pluripotent stem cells in vivo.

Using lineage-tracing experiments in mice, we found that a Runx1 enhancer element, eR1, promotes its expression in the isthmus stem cells of stomach corpus as well as pyloric gland in the antrum. We were able to use eR1 to express oncogenic mutations in gastric stem cells, proving a new model for studies of gastric carcinogenesis.

Pulses play a significant role in nitrogen cycling as they fix atmospheric N 2 through symbiosis. However, it is unknown whether there are differences in the ability of biological nitrogen fixation (BNF) among pulse species and individual cultivars. Here, we quantified the BNF ability of selected pulse cultivars and determined the effect on crop yield. A total of 25 species-cultivar combinations of chickpea (Cicer arietinum L.), dry bean (Phaseolus vulgaris L.), faba bean (Vicia faba L.), field pea (Pisum sativum L.), and lentil (Lens culinaris Medik.) were tested in 2008-2010. Pulses had a higher BNF in the wetter 2010 season, and a lower BNF in the drier 2009 season. In 2010, faba bean and chickpea had the highest BNF at 106 kg N ha −1 , followed by lentil, field pea, and dry bean at 87, 69, and 12 kg N ha −1 , respectively. Across years, field pea had the most stable BNF ability, fixing 55 kg N ha −1 with an average seed yield of 2418 kg ha −1. There are large differences in BNF and yield among cultivars within a species and the magnitude of the difference varied with years. Large genetic variability in BNF and yield suggest the possibility that pulse cultivars with a higher N 2-fixing ability and seed yield can be developed through selection of the N 2-fixing trait.