Project description:Attenuation of Hedgehog (Hh) pathway activity leads to accelerated tumor progression in a mouse model of N-butyl-N-4-hydroxybutyl nitrosamine (BBN) – induced bladder carcinoma. In order to identify genes regulated by the Hh pathway that might be involved in bladder cancer progression, we performed transcriptional profiling of bladders harvested from mice after BBN-exposure, comparing Gli1CreER/WT; Smoflox/WT mice to Gli1CreER/WT; Smoflox/flox mice, which express CreER under control of the Gli1 promoter and carry one or two floxed alleles of the essential Hh pathway transductory component Smoothened (Smo) respectively. Administration of Tamoxifen to these mice results in attenuation of Hh pathway activty to a greater extent in the Gli1CreER/WT;Smoflox/flox mice as compared to Gli1CreER/WT;Smoflox/WT mice, allowing identification of Hh-pathway regulated genes. 6 total samples were analyzed. 3 bladders from Gli1CreER/WT; Smoflox/WT mice and 3 bladders from Gli1CreER/WT; Smoflox/flox mice were analyzed.
Project description:Attenuation of Hedgehog (Hh) pathway activity leads to accelerated tumor progression in a mouse model of N-butyl-N-4-hydroxybutyl nitrosamine (BBN) – induced bladder carcinoma. In order to identify genes regulated by the Hh pathway that might be involved in bladder cancer progression, we performed transcriptional profiling of bladders harvested from mice after BBN-exposure, comparing Gli1CreER/WT; Smoflox/WT mice to Gli1CreER/WT; Smoflox/flox mice, which express CreER under control of the Gli1 promoter and carry one or two floxed alleles of the essential Hh pathway transductory component Smoothened (Smo) respectively. Administration of Tamoxifen to these mice results in attenuation of Hh pathway activty to a greater extent in the Gli1CreER/WT;Smoflox/flox mice as compared to Gli1CreER/WT;Smoflox/WT mice, allowing identification of Hh-pathway regulated genes.
Project description:The brown anole lizard, Anolis sagrei, is an emerging squamate model for developmental and functional genetic studies. To develop additional tools and resources for mechanistic studies of signaling pathways and cellular processes in A. sagrei, we established an in vitro system. Using this approach, we studied Hedgehog (Hh) signaling, one of the key developmental signaling pathways, which has evolved across the metazoa. We investigated Hh pathway-induced transcriptional changes in two evolutionarily distinct tetrapods: A. sagrei, and M. musculus, to identify the species-specific and evolutionarily shared responses. We report that ~45 % of genes induced as a response to Hh pathway activation in A. sagrei, are shared with M. musculus. To further increase the versatility of A. sagrei as a squamate model system for gene editing and genomic studies, we established and characterized a new immortalized A. sagrei embryonic fibroblast cell line ASEC-1. We performed whole-genome sequencing analysis to annotate the set of polymorphisms within this cell line. We conclude that transcriptome characterization of the ASEC-1 cell line would permit further investigations dissecting the complex biological and evolutionary aspects of Hh signaling.
Project description:Mice bearing primary human chondrosarcoma xenografts were treated with IPI 926, and mRNA levels of known Hh pathway genes and endpoint tumor volumes were measured. Gene expression profiling of IPI-926 treated tumors was conducted to identify potential novel Hh target genes.
Project description:The objective of this study was to evaluate the efficacy of nicotinamide in a N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced urinary bladder cancer model in mice, and to identify through gene expression profiling the molecular signatures of cancer prevention by nicotinamide. We used 20 mice for microarray experiments: five mice with normal bladders (group I), five with nicotinamide-treated bladders (group II), five with BBN-induced mouse bladder tumors (group III), and five with non-tumorigenic bladders treated with BBN and nicotinamide (group IV). Keywords: Gene expression, Mouse bladder cancer, Cancer prevention
Project description:Mice bearing primary human chondrosarcoma xenografts were treated with IPI 926, and mRNA levels of known Hh pathway genes and endpoint tumor volumes were measured. Gene expression profiling of IPI-926 treated tumors was conducted to identify potential novel Hh target genes. 4 Control treated and 4 IPI-926 treated NSG Mice. Primary tumor was obtained from a single chondrosarcoma patient.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:Epithelial Hedgehog (Hh) ligands regulate several aspects of fetal intestinal organogenesis and emerging data implicate the Hh pathway in inflammatory signaling in adult colon. We investigated the effects of chronic Hh inhibition in vivo and profiled molecular pathways acutely modulated by Hh signaling in the intestinal mesenchyme. Experiment Overall Design: E18.5 intestinal mesenchyme was isolated and cultured. Mesenchyme was treated with Sonic (Shh) or Indian (Ihh) hedgehog ligand or Vehicle (control) acutely to identify targets regulated by Hh signaling in intestinal mesenchyme.
