Project description:Mammary gland branching morphogenesis is thought to depend on the mobilization of the membrane-anchored matrix metalloproteinases, MT1-MMP and MT2-MMP, that drive epithelial cell invasion by remodeling the extracellular matrix and triggering associated signaling cascades. However, the roles that these proteinases play during mammary gland development in vivo remains undefined. A mammary gland branching program that occurs during the first 10 days of early postnatal development was used to characterize the impact of global Mt1-mmp or Mt2-mmp targeting on mammary gland morphogenesis. Transcriptome profiling of ductal networks and associated stroma was used to investigate the functional roles of MT1-MMP in the early postnatal mammary gland in an unbiased fashion.
Project description:Mammary gland branching morphogenesis is thought to depend on the mobilization of the membrane-anchored matrix metalloproteinases, MT1-MMP and MT2-MMP, that drive epithelial cell invasion by remodeling the extracellular matrix and triggering associated signaling cascades. However, the roles that these proteinases play during mammary gland development in vivo remains undefined. A mammary gland branching program that occurs during the first 10 days of early postnatal development was used to characterize the impact of global Mt1-mmp or Mt2-mmp targeting on mammary gland morphogenesis. Transcriptome profiling of ductal networks and associated stroma was used to investigate the functional roles of MT2-MMP in the early postnatal mammary gland in an unbiased fashion.
Project description:Mammary gland branching morphogenesis is thought to depend on the mobilization of proteolytic machinery from the matrix metalloproteinase (MMP) family, namely MT1-MMP/MMP14, to drive coordinated epithelial cell invasion through the interstitial extracellular matrix, but the dominant effector has remained undefined. Unexpectedly, we find MMP14 controls postnatal mammary gland branching from the periductal stroma. Transcriptome profiling of stromal cell-targeted mammary glands was used to characterize the impact of stromal Mmp14-targeting on the growth factor and signaling cascades implicated in mammary gland morphogenesis. Transcriptome profiling of ductal networks and associated stroma was used to investigate the functional roles of MMP14 in the postnatal mammary gland stroma in an unbiased fashion.
Project description:Mammary gland branching morphogenesis is thought to relie on the mobilization of the membrane-anchored matrix metalloproteinase, Mmp14/MT1-MMP, to drive mammary epithelial invasion by remodeling the extracellular matrix and triggering associated signaling cascades. However, the roles that this proteinase plays during postnatal mammary gland development in vivo remain undefined. A mammary gland branching program that occurs during the first 4 weeks of postnatal mouse development, in tandem with recently developed Mmp14-floxed mice and MMTV-Cre transgenics that express Cre recombinase throughout the mammary epithelial cell compartment, were used to characterize the impact of deleting epithelial cell Mmp14 on mammary gland morphogenesis. Transcriptome profiling of mammary epithelial cells was used to investigate the functional roles of MT1-MMP in the postnatal mammary epithelial cell compartment in an unbiased fashion
Project description:Mammary gland branching morphogenesis is thought to relie on the mobilization of the membrane-anchored matrix metalloproteinase, Mmp14/MT1-MMP, to drive mammary epithelial invasion by remodeling the extracellular matrix and triggering associated signaling cascades. However, the roles that this proteinase plays during postnatal mammary gland development in vivo remain undefined. A mammary gland branching program that occurs during the first 4 weeks of postnatal mouse development, in tandem with recently developed Mmp14-floxed mice and MMTV-Cre transgenics that express Cre recombinase throughout the mammary epithelial cell compartment, were used to characterize the impact of deleting epithelial cell Mmp14 on mammary gland morphogenesis. Transcriptome profiling of mammary epithelial cells was used to investigate the effects of MMTV-Cre expression on the postnatal mammary epithelial cell compartment in an unbiased fashion
Project description:VSMC-specific MT1-MMP gene targeting in APOE-null mice promotes atherosclerosis and iliac artery aneurysm formation. To determine the MT1-MMP-dependent regulation of VSMC function, whole-genome transcriptomes of wild-type and MT1-MMP-null APOE-null VSMCs were determined. We used microarray-based transcriptome analysis to detect MT1-MMP-dependent regulation of VSMC function under atherogenic conditions.