Inhibitory BMO signaling controls mammalian renal branching morphogenesis in vivo

by Sunny Sun-Hee Hartwig

Written in English
Published: Pages: 157 Downloads: 154
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In this thesis I investigated the role of the inhibitory Bmp signaling pathway during mouse kidney renal development using (i) genetic haploinsufficiency models to investigate the functions of Bmp2 and Gpc3-Bmp2 interactions during renal development in vivo and (ii) conditional Alk3 loss-of-function in the UB lineage to investigate the function of Alk3-dependent Bmp signaling during RBM in vivo.During embryonic development, the collecting duct system of the kidney arises through iterative growth and branching of the ureteric bud (UB) and daughter collecting ducts, a process termed renal branching morphogenesis (RBM). Previous work in our lab identified an inhibitory ALK3-dependent BMP signaling pathway that controls cellular and morphogenetic events during RBM in vitro and in transgenic over-expression mouse models. However, the early embryonic lethality of homozygous Bmp2-/- and Alk3-/- mice has precluded complementary conventional loss-of-function studies to define the role of Bmp signaling during renal development in vivo.Results from this thesis provide the first genetic evidence that an inhibitory Bmp2 signaling pathway controls UB cell proliferation and branching during RBM in vivo, and that Bmp2 signaling is genetically modulated by Gpc3. Further, these results demonstrate an essential requirement of ALK3-dependent Bmp signaling for normal kidney development in vivo, and identify a critical architectural role for ALK3 in establishing and maintaining the primary UB branching pattern.

Edition Notes

StatementSunny Sun-Hee Hartwig.
The Physical Object
Paginationxvi, 157 leaves.
Number of Pages157
ID Numbers
Open LibraryOL19758381M
ISBN 109780494159293

  A molecular key to aging of the blood and immune system has been discovered in new research conducted at UC San Francisco, raising hope that it may be possible to find a way to slow or reverse the growing risk for aging-associated chronic inflammatory diseases, anemia, blood cancers, and life-threatening infections. Notch signaling drives multiple myeloma induced osteoclastogenesis. PDF tissue patterning and morphogenesis and is dysregulated To confirm the crucial role of Notch signaling in MM-associated bone disease ex vivo, we inhibited the Notch signaling during the differentiation of primary human monocytes induced by Cited by: New targets and strategies for offsetting the effect of obesity on cancer risk are urgently needed. In the present study, we examined the effect of dietary energy balance manipulation on steady-state signaling in multiple epithelial tissues, with a focus on the Akt and mammalian target of rapamycin (mTOR) by: Activated NF-κB has been detected in endothelial cells, smooth muscle cells, and macrophages in atherosclerotic plaques. NF-κB is a family of transcription factors consisting of five members: p65 (relA), c-Rel, relB, p50, and p These proteins form homo- or Cited by:

  Array-based hybridization experiments and analysis of expression profiles. We compared gene expression in C. elegans wild type to that of animals mutant for the TGFβ pathway genes daf-7 (ligand; [5, 6]), daf-8 and daf (Smad transcription factors; [8, 16]).At 25°, these daf-c mutants form an L2d instead of the L2 larva, and begin dauer morphogenesis after the L2d to dauer by:   Most cases (~97%) are caused by haploinsufficiency of Notch signaling pathway, mostly due to mutations or (less often) locus deletions of the JAGGED1 gene (20pp12). Very rarely (Cited by: 5.   Autophagy is a highly conserved pathway that recycles cytosolic material and organelles via lysosomal degradation. Once simplistically viewed as a non-selective survival strategy in dire straits, autophagy has emerged as a tightly regulated process ensuring organelle function, proteome plasticity, cell differentiation and tissue homeostasis, with key roles in physiology and by: 8. 70 S.-Y. Su et al. / Journal of Ethnopharmacology () 68–73 hydrogen peroxide in methanol for 15min and the non-specific binding was blocked with 1% bovine serum albumin at room temperature for 1h. Sections were incubated with mouse mono-.

T1 - CD99 regulates neural differentiation of Ewing sarcoma cells through MIRa-Notch-mediated control of NF-κB signaling AU - Ventura, S. AU - Aryee, D. N TCited by: Renal Ischemic injury model: Groups of seven to eight week old C57BL/6 mice (n =5–10) under anesthesia underwent unilateral renal pedicle clamping for 35 min followed by reperfusion for 24 h, 5 days and 10 days as a model of ischemia-reperfusion as described [19 –21]. Throughout the procedure, body temperatures were main-Cited by: 2.   IGFBP-2 represents a multifunctional protein with effects on growth, reproductive development, aging, and metabolism. For the expression of these diverse effects in vivo, IGFBP-2 has a number of binding sites for IGFs, integrins, and order to assess the relative contributions of these binding sites to the multiple effects of IGFBP-2, we have developed transgenic mouse models Author: Andreas Hoeflich, Anja Reyer, Nancy Schindler, Daniela Ohde, Elisa Wirthgen, Julia Brenmoehl. Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 mutation, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl) in the mouse using several Cre drivers.

Inhibitory BMO signaling controls mammalian renal branching morphogenesis in vivo by Sunny Sun-Hee Hartwig Download PDF EPUB FB2

The role of Fgf signaling in branching morphogenesis of the mammalian kidneys is not as well known as in the lungs (reviewed in Blake & Rosenblum, ; Costantini & Kopan, ).

Yet, Fgf7-null. Branching morphogenesis, defined as the growth and branching of epithelial tubules, is a fundamental developmental process involved in the formation of a variety of mammalian tissues, including the kidney.

Defective renal branching may result in a number of clinically relevant abnormalities, including renal agenesis, renal dysplasia, multiplex kidneys, and by:   Branching morphogenesis assays.

Branching morphogenesis was induced using slight modifications of previously published protocols (Hirai et al., ; Simian et al., ).Cell clusters were prepared as follows: EpH4 cells suspended in growth medium containing DNase I were placed on top of agarose-coated wells and incubated at rpm and 37°C on an orbital shaker overnight, yielding Cited by:   Abstract.

The sex of an individual is determined by the fate of the gonad. While the expression of Sry and Sox9 is sufficient to induce male development, we here show that female differentiation requires activation of the canonical β-catenin signaling pathway.

β-catenin activation is controlled by Rspo1 in XX gonads and Rspo1 knockout mice show masculinized by: HGF mediates branching morphogenesis in renal epithelial cells by activating c-met, which then sets into motion a series of downstream signaling pathways.

Our laboratory and others have shown that HGF-induced cell migration and branching morphogenesis are dependent on activation of both the Erk and phosphatidylinositol 3-kinase (PI3-K Cited by:   A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs).

There is some evidence that these ECM cues affect Cited by: Methods. Treatment with DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) or ANIT (alpha-naphthyl-isothiocyanate) was used to induce biliary damage in wild type mice and in mice with a liver specific defect in the Notch-2 receptor (NotchcKO) or in c progenitor cells, ductular reaction, and mature ductules were quantified using K19 and SOXCited by:   Vascular calcification (VC) is a major risk factor for cardiovascular mortality in chronic renal failure (CRF) patients, but the pathogenesis remains partially unknown and effective therapeutic targets should be urgently explored.

Here we pursued the therapeutic role of rapamycin in CRF-related VC. Mammalian target of rapamycin (mTOR) signal was activated in the aortic wall of CRF by: Betlienda, Maryland 20K!^ Accepted April 8, S Branching morphogenesis in the mammary gland involves focal regions of cell proliferation, the terminal and lateral ductal buds, that exist simultaneously with extensive regions of differentiated ducts in which budding and growth are actively by: for tissue morphogenesis during fetal development (18–20) and tumor metastasis in adults (19–23).

Hedgehog (Hh) family ligands regulate EMT during the latter circumstances (22, 24–29). Hh signaling controls tissue construction and remodeling by. PBRM1 Regulates the Expression of Genes Involved in Metabolism and Cell Adhesion in Renal Clear Cell Carcinoma.

Chowdhury B, Porter EG, Stewart JC, Ferreira CR, Schipma MJ, Dykhuizen EC PLoS One. Apr 21;11(4):e doi: / eCollection In order to determine if a role existed for Y in mediating CTLA-4 inhibitory signaling in vivo, we studied lymphocyte activation and homeostasis in CTLA-4‐/‐ mice that were reconstituted.

Follicular growth and differentiation are tightly regulated by endocrine, autocrine, and paracrine factors ().The coordinated biosynthesis of steroids in the ovary is critical for reproductive cycle, successful ovulation, and eventual pregnancy ().FSH-induced synthesis of progesterone and estradiol involves the regulation of various steroidogenic enzymes, such as steroidogenic acute regulatory Cited by:   Read "Recombinant leukemia inhibitory factor suppresses human medullary thyroid carcinoma cell line xenografts in mice, Cancer Letters" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.

Sensitivity to an inhibitor of IκB, as well as inhibition of an NF-κB gene expression signature demonstrated the importance of NF-κB signaling for chordoma growth. This serially transplantable chordoma xenograft is thus a practical model to study chordomas and perform in vivo. Fgf3 is rapidly induced after vHnf1 overexpression.

Previous work indicated that Fgf3 was downstream of vHnf1 in the induction of caudal rhombomeric markers such as Krox20 and 1 operates in a specific time-window and is not able to induce Fgf3, MafB or Krox20 at late stages of hindbrain patterning [].One important question was to know whether Fgf3 was a direct downstream target of by: Tumor necrosis factor 01 (TNF)’ is a cytokine that appears to have a key role in orchestrating the inflammatory response.

TNF, by affecting many target cell types, is capable of induc- ing a wide spectrum of proinflammatory activities and has * This work was supported by. Notch signaling is a well-conserved cell-fate determining factor in embryo development, and the dyregulation of this signaling is frequently observed in many types Cited by: 3.

The function of macrophage inhibitory cytokine-1 (MIC-1) in cancer remains controversial, and its signaling pathways re-main poorly understood. In this study, we demonstrate that MIC-1 induces the transactivation of EGFR, ErbB2, and ErbB3 through the activation of c-Src in SK-BR-3 breast cells.

MIC In the current review, we discuss the role of NF-κB and JAK/STAT signaling pathways and their small molecule regulators in the therapy of inflammatory diseases. Considering potential harmful effects directly assigned to the COX-2 inhibition, novel therapeutically-relevant biological targets such as NF-κB and JAK/STAT signaling pathways have.

Western Blotting Protocol. For western blots, incubate membrane with diluted primary antibody in 5% w/v BSA, 1X TBS, % Tween ® 20 at 4°C with gentle shaking, overnight. NOTE: Please refer to primary antibody datasheet or product webpage for recommended antibody dilution.

Solutions and ReagentsCategory: Primary Antibodies. UC students create UV box to aid Crossroad Health Center in Ap Dis-Box is an ultraviolet box designed by a group of University of Cincinnati engineering students that may help extend use of personal protective equipment (PPE) for healthcare workers at Cincinnati’s Crossroad Health Center.

Recent studies have reported that NF-κB mediated down-regulation of miRNA and lower expression of miRNA promoted the deposition of collagens in fibrotic liver.

Our previous research demonstrated that the increased Hedgehog (Hh) signaling, a key regulator for hepatic fibrogenesis, induced the severe hepatic fibrosis in the livers with impaired NF-κB by: Hh signaling also controls the migration of basal epidermal cells to more superficial aspects of adult skin (63, 64).

Thus, the new evidence for Hh-mediated induction of EMT in some bile duct epithelial cells during chronic biliary injury suggests that migration of these cells might be involved in remodeling of adult livers with cholestatic by:   A research team at the Walter and Eliza Hall Institute, led by Associate Professor Guillaume Lessene, will test in preclinical models how cancer cells respond to treatment with the Mcl signaling is important for radiation‑induced cell apoptosis and autophagy (27).

The present study used a novel recombinant protein, namely flagellin A (FlaA) N/C, which was developed in an earlier study and is derived from the flagellinprotein of Legionella pneumophila (28). FlaA N/C has been shown to. Death receptors (DRs) play an important role in renal pathology.

We have shown that DR3 is inducibly expressed on renal tubular epithelial cells in the setting of inflammatory injuries. In this study we investigate the expression of DR3 in renal endothelial cells and their response to TL1A, the only known ligand of DR3.

We did RT-PCR, flow cytometry and subcellular immunoblotting to examine. Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin. V M Dixit, S Green, V Sarma, L B Holzman, F W Wolf, K O'Rourke, P A Ward. PBRM1 regulates the expression of genes involved in metabolism and cell adhesion in renal clear cell carcinoma.

chromatin remodeling complex and is the second most frequently mutated gene in clear-cell renal cell Carcinoma (ccRCC). Mutation of PBRM1 is believed to be an early event in carcinogenesis, however its function as a tumor Cited by: activation of multidrug resistance (MDR) in NF-κB signaling cascade of SLCICs was studied to judge its role as an inhibitor of NF-κB.

To the best of our knowledge this is one of the first studies where efficacy of BRM as an anticancer product under in vitro and in vivo. produced in the thymus, TGF- 1 signaling combined with T-cell receptor signaling induces the expression of Foxp3 in CD4 T cells in the periphery.

We found that ICAM-1 / mice have fewer T regulatory cells in the periphery than WT controls, due to a role for ICAM-1 in induction of Foxp3 expression in Cited by: 1bwf: escherichia coli glycerol kinase mutant with bound atp analog showing substantial domain motionCited by: the mammalian ovary.

However, due to limitations of research tools—such as the lackof asuitable promoterthat specifically targets pfGCs in vivo—whether and how the somatic pfGCs might regulate the activation of primordial follicles and contribute to the awakening of dormant oocytes in the mammalian ovary are unknown.