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112 results (0.01 seconds)
  • person: Susan Mango
  • University of Basel; Basel, Switzerland
  • paper:
  • [
    Curr Biol,
    2009]
    Susan Mango is Benning Professor of Oncological Sciences at the University of Utah and an Investigator at the Huntsman Cancer Institute. She grew up in England and Washington D.C. before attending Harvard University. She received her Ph.D. from Princeton, where she studied the c-myc oncogene with Michael Cole. She was introduced to the nematode Caenorhabditis elegans as a postdoc with Judith Kimble at the University of Wisconsin - Madison, and moved to Utah in 1996 to start her own lab. After 13 years at the University of Utah, she will move to Harvard University in July 2009. Her principal focus is transcriptional strategies of organ development, using the C. elegans foregut as a model.
  • paper:
  • [
    Development & Evolution Meeting,
    2008]
    No abstract submitted
  • paper:
  • [
    WormBook,
    2007]
    The C. elegans foregut (pharynx) has emerged as a powerful system to study organ formation during embryogenesis. Here I review recent advances regarding cell-fate specification and epithelial morphogenesis during pharynx development. Maternally-supplied gene products function prior to gastrulation to establish pluripotent blastomeres. As gastrulation gets under way, pharyngeal precursors become committed to pharyngeal fate in a process that requires PHA-4 /FoxA and the Tbox transcription factors TBX-2 , TBX-35 , TBX-37 and TBX-38 . Subsequent waves of gene expression depend on the affinity of PHA-4 for its target promoters, coupled with combinatorial strategies such as feed-forward and positive-feedback loops. During later embryogenesis, pharyngeal precursors undergo reorganization and a mesenchymal-to-epithelial transition to form the linear gut tube. Surprisingly, epithelium formation does not depend on cadherins, catenins or integrins. Rather, the kinesin ZEN-4 /MKLP1 and CYK-4 /RhoGAP are critical to establish the apical domain during epithelial polarization. Finally, I discuss similarities and differences between the nematode pharynx and the vertebrate heart.
  • antibody: WBAntibody00001381
  • Antibody PGL-1, provided by Susan Strome. pgl-1
  • antibody: WBAntibody00002118
  • Mouse monoclonal antibody J67, from Susan Strome.
  • antibody: WBAntibody00001746
  • Antibody against cuticle, provided by Susan Strome
  • antibody: WBAntibody00001623
  • Antibody against PGL-1, provided by Susan Strome. pgl-1
  • antibody: WBAntibody00000859
  • Rabbit antibody against PGL-1. Provided by Susan Strome. pgl-1
  • paper:
  • [
    International Worm Meeting,
    2011]
    The PHA-4/FoxA forkhead transcription factor in nematodes plays an integral role in all aspects of pharyngeal development, from the earliest specification of pharyngeal precursors to the determination of definitive cell types (1-3). Previous studies in the Mango lab have suggested that PHA-4 activates the expression of many pharyngeal genes directly (4). Our previous studies revealed that binding site affinity for PHA-4 contributes to target diversity in vivo. In fact, the affinity between PHA-4 and its target promoters contributes to the timing of gene expression (4). Mutation of a high affinity PHA-4 binding site to a lower affinity site results in a later onset of expression; conversely, switching a low affinity site to a higher affinity advances gene activation (4). However, the exact mechanism by which PHA-4 temporally regulates all of its targets through binding site affinity remains unclear. To address this question, we employed the NSA (Nuclear Spot Assay) which uses LacO/LacI::CFP to mark pseudochromosome arrays and PHA-4::YFP to track pha-4 (5-7). By tracking both YFP and CFP signals and their distributed domains in the nucleus, we can follow patterns of association between PHA-4 and its target promoters in living embryos with precise spatial and temporal resolution. Our data indicate that PHA-4::YFP binds to target promoters hours before the transcription firing and that the level of PHA-4::YFP association is significantly different between high versus low affinity sites at early embryonic stages. In addition, manipulation of PHA-4 levels at early embryonic stages (2E to 8E) by heatshock (over expression) or RNAi (reduced expression) can alter the onset of pharyngeal expression. These data suggest that PHA-4 binds to pharyngeal target promoters through different affinity sites at early embryonic stages and this binding may prime the timing of gene expression at later stages. We will further investigate the PHA-4 occupancy at endogenous loci during development by chromatin immunoprecipitation. Together, this study will help clarify how binding site affinity influences temporal regulation of transcription. Reference 1.Mango S.E., Lambie E.J., and Kimble J. Development 120 : 3019. (1994) 2.Horner M., Quintin S., Domeier M.E., Kimble J., Labouesse M. and Mango S.E. Gene & Development 12:1947. (1998). 3.Gaudet J., Muttumu S., Horner M., and Mango S.E. PLoS Biol 2 : e352. (2004) 4.Gaudet J., and Mango S.E. Science 295 : 821. (2002) 5.Carmi I., JKopczynski J.B. and Meyer B.J. Nature 396:168. (1998) 6.Belmont A.S., Straight A.F. Trends Cell Biol 8:121. (1998) 7.Fakhouri T.H., Stevenson J., Chisholm A.D., Mango S.E. PLos Genet 6: e1001060. (2010).
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