CONTROL OF EARLY DEVELOPMENT IN C ELEGANS

Summary

Principal Investigator: Susan Strome
Affiliation: University of California
Country: USA
Abstract: A crucial process in the development of every multicellular organism is the specification of different developmental fates in different cells of the early embryo. In embryos of the nematode Caenorhabditis elegans, as in embryos of many other species, this process is thought to be controlled mainly by maternally supplied factors that are differentially partitioned during the early divisions of the zygote. In addition to maternal factors, we have new evidence that paternally supplied factors also are required for normal early development. We propose to combine genetic, molecular, and cell biological approaches to identify crucial maternal and paternal factors, learn how lineage-specific factors are differentially partitioned to specific cells, and elucidate when and how such factors participate in cell-fate determination in C. elegans embryos. We have identified a novel paternal effect embryonic lethal mutant, spe- 11, that demonstrates that a sperm-contributed factor is required for normal zygote development. Two exciting possibilities are that the spe- 11 product activates the oocyte or provides polarity to the zygote. To investigate the role of the spe-11 product, we will clone the spe-11 gene and analyze and localize its gene product, define the temperature- sensitive period of the mutant, isolate second site suppressors, and try to rescue mutant zygotes by microinjecting sperm factors. The maternally supplied factors on which we will focus are those required for germ-line development. P granules, which are maternally supplied cytoplasmic structures that are segregated to the germ-line blastomeres during the early divisions, are excellent candidates for germ-line "determinants". We are using biochemcal techniques and our collection of anti-P-granule antibodies to purify and analyze the composition of the granules; our long-term goal is to assess their function in the germ line through genetics. Concurrently, by screening for maternal effect sterile of grand-childless mutants, we are identifying mutants defective in maternal control of germ-line development; some of these may identify the factors that determine the germ line. Finally, we are continuing our analysis of the mechanism of segregation of lineage-specific factors. We have already demonstrated that microfilaments (MFs) play a critical role in the generation of zygotic polarity and in segregating P granules to the germ lineage. We will investigate the role of MFs in partitioning somatic-lineage-specific factors, and we will investigate several specific mechanisms by which MFs could participate in segregation events, such as actin-myosin interactions and cytoplasmic streaming.
Funding Period: 1984-09-01 - 1992-03-31
more information: NIH RePORT

Top Publications

  1. pmc Germ-Granule Components Prevent Somatic Development in the C. elegans Germline
    Dustin L Updike
    Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA Kathryn W Davis Center for Regenerative Biology and Medicine, Mount Desert Island Biological Laboratory, Salisbury Cove, ME 04672, USA Electronic address
    Curr Biol 24:970-5. 2014
  2. pmc Opposing activities of DRM and MES-4 tune gene expression and X-chromosome repression in Caenorhabditis elegans germ cells
    Tomoko M Tabuchi
    Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605
    G3 (Bethesda) 4:143-53. 2014
  3. pmc Antagonism between MES-4 and Polycomb repressive complex 2 promotes appropriate gene expression in C. elegans germ cells
    Laura J Gaydos
    Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, USA
    Cell Rep 2:1169-77. 2012
  4. pmc Trans-generational epigenetic regulation of C. elegans primordial germ cells
    Hirofumi Furuhashi
    Biology Department, Emory University, Atlanta, GA 30322, USA
    Epigenetics Chromatin 3:15. 2010
  5. pmc A spatial and temporal map of C. elegans gene expression
    W Clay Spencer
    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee 37232, USA
    Genome Res 21:325-41. 2011
  6. pmc P granules extend the nuclear pore complex environment in the C. elegans germ line
    Dustin L Updike
    Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, USA
    J Cell Biol 192:939-48. 2011
  7. pmc The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny
    Andreas Rechtsteiner
    Department of Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America
    PLoS Genet 6:e1001091. 2010
  8. pmc Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are differentially required for histone H3 Lys 4 methylation in embryos and adult germ cells
    Yu Xiao
    Laboratory of Molecular and Cellular Biology, UMR5239 CNRS, Ecole Normale Superieure de Lyon, 69007 Lyon, France
    Proc Natl Acad Sci U S A 108:8305-10. 2011
  9. pmc P granule assembly and function in Caenorhabditis elegans germ cells
    Dustin Updike
    Molecular Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA 95064, USA
    J Androl 31:53-60. 2010
  10. pmc SLIT/ROBO1 signaling suppresses mammary branching morphogenesis by limiting basal cell number
    Hector Macias
    Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, 95064, USA
    Dev Cell 20:827-40. 2011

Scientific Experts

  • WILLIAM T SULLIVAN
  • Laurel B Bender
  • Susan Strome
  • Dustin L Updike
  • Andreas Rechtsteiner
  • Teruaki Takasaki
  • Thea A Egelhofer
  • Valerie Reinke
  • Caroline A Spike
  • Tomoko M Tabuchi
  • Laura J Gaydos
  • Hector Macias
  • Yu Xiao
  • Lisa N Petrella
  • W Clay Spencer
  • Wenchao Wang
  • Hirofumi Furuhashi
  • Steve Dunkelbarger
  • Dustin Updike
  • Hiroshi Kimura
  • Melissa A Henderson
  • Jiyoung Kim
  • Caroline Spike
  • Roger Albertson
  • Diane J Schmidt
  • Carrie S Ketel
  • Andrew Kekūpa a Knutson
  • Anne C Campbell
  • Kirsten A Hagstrom
  • Coleen R Carroll
  • Vipin T Sreedharan
  • Angel Moran
  • Stefan R Henz
  • Stephanie J Hachey
  • Gwen Soete
  • Kathie L Watkins
  • David M Miller
  • Shai Shaham
  • LISA PETRELLA
  • Hendrik C Korswagen
  • Gwyndolen Harburg
  • Cédric Rakotomalala
  • Lindsay Hinck
  • Valérie J P Robert
  • Jennifer E Compton
  • Sarah Petersen
  • JOSEPH D WATSON
  • Christian Widmer
  • Francesca Palladino
  • Mélissa Moreno
  • Yazeed Samara
  • Cecile Bedet
  • Menachem Katz
  • Stephen E Von Stetina
  • Phyllis Strickland
  • Rebecca D McWhirter
  • Jeremy Kreher
  • Gunnar Rätsch
  • Jeanyoung Jo
  • Thomas Simonet
  • Georg Zeller
  • William G Kelly
  • Sevinc Ercan
  • Paula M Checchi
  • Jason D Lieb
  • Taryn M Phippen
  • Tengguo Li
  • Vince Contreras
  • Ah Reum Lee
  • Yhong Hee Shim
  • Elizabeth Cronland
  • Brett D Keiper
  • Ichiro Kawasaki
  • Jian Cao
  • April Orsborn
  • Jason Bader
  • Nicole Meyer
  • Erica Racen
  • Tao Shih Hsieh
  • Kathleen Kuznicki
  • Karen Bennett
  • Christopher Yee
  • Jay Kirchner
  • Hiroshi Sakamoto
  • Kiyoji Nishiwaki
  • Zheng Liu
  • Jun Ichi Nakayama
  • Yasuaki Habara
  • Kunio Inoue
  • Erica F Andersen

Detail Information

Publications22

  1. pmc Germ-Granule Components Prevent Somatic Development in the C. elegans Germline
    Dustin L Updike
    Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA Kathryn W Davis Center for Regenerative Biology and Medicine, Mount Desert Island Biological Laboratory, Salisbury Cove, ME 04672, USA Electronic address
    Curr Biol 24:970-5. 2014
    ..We found that compromising P granules causes germ cells to express neuronal and muscle markers and send out neurite-like projections, suggesting that P granules maintain totipotency and germline identity by antagonizing somatic fate. ..
  2. pmc Opposing activities of DRM and MES-4 tune gene expression and X-chromosome repression in Caenorhabditis elegans germ cells
    Tomoko M Tabuchi
    Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605
    G3 (Bethesda) 4:143-53. 2014
    ..Our study reveals that conserved transcriptional regulators implicated in development and cancer counteract each other to fine-tune transcript dosage. ..
  3. pmc Antagonism between MES-4 and Polycomb repressive complex 2 promotes appropriate gene expression in C. elegans germ cells
    Laura J Gaydos
    Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, USA
    Cell Rep 2:1169-77. 2012
    ..This antagonism ensures proper patterns of gene expression for germ cells, which includes repression of somatic genes and the X chromosomes...
  4. pmc Trans-generational epigenetic regulation of C. elegans primordial germ cells
    Hirofumi Furuhashi
    Biology Department, Emory University, Atlanta, GA 30322, USA
    Epigenetics Chromatin 3:15. 2010
    ..abstract:..
  5. pmc A spatial and temporal map of C. elegans gene expression
    W Clay Spencer
    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee 37232, USA
    Genome Res 21:325-41. 2011
    ....
  6. pmc P granules extend the nuclear pore complex environment in the C. elegans germ line
    Dustin L Updike
    Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, CA 95064, USA
    J Cell Biol 192:939-48. 2011
    ..Our results suggest that P granules extend the NPC environment in the germ line and provide insights into the roles of the PGL and GLH family proteins...
  7. pmc The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny
    Andreas Rechtsteiner
    Department of Molecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America
    PLoS Genet 6:e1001091. 2010
    ..We propose that MES-4 transmits the memory of gene expression in the parental germ line to offspring and that this memory role is critical for the PGCs to execute a proper germline program...
  8. pmc Caenorhabditis elegans chromatin-associated proteins SET-2 and ASH-2 are differentially required for histone H3 Lys 4 methylation in embryos and adult germ cells
    Yu Xiao
    Laboratory of Molecular and Cellular Biology, UMR5239 CNRS, Ecole Normale Superieure de Lyon, 69007 Lyon, France
    Proc Natl Acad Sci U S A 108:8305-10. 2011
    ..This study demonstrates that individual subunits of SET1-related complexes can show tissue specificity and developmental regulation and establishes C. elegans as a model to study SET1-related complexes in a multicellular organism...
  9. pmc P granule assembly and function in Caenorhabditis elegans germ cells
    Dustin Updike
    Molecular Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA 95064, USA
    J Androl 31:53-60. 2010
    ..The findings in C elegans have important implications for the germ granule function during postnatal germ cell differentiation in mammals...
  10. pmc SLIT/ROBO1 signaling suppresses mammary branching morphogenesis by limiting basal cell number
    Hector Macias
    Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, 95064, USA
    Dev Cell 20:827-40. 2011
    ..Together, our studies provide mechanistic insight into how specification of basal cell number influences branching morphogenesis...
  11. pmc synMuv B proteins antagonize germline fate in the intestine and ensure C. elegans survival
    Lisa N Petrella
    Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA 95064, USA
    Development 138:1069-79. 2011
    ..Somatic expression of germline genes is enhanced at elevated temperature, leading to developmentally compromised somatic cells and arrest of newly hatched larvae...
  12. pmc MRG-1, an autosome-associated protein, silences X-linked genes and protects germline immortality in Caenorhabditis elegans
    Teruaki Takasaki
    Department of Biology, Graduate School of Science and Technology, Kobe University, 1 1 Rokkodaicho, Nadaku, Kobe 657 8501, Japan
    Development 134:757-67. 2007
    ..We discuss how an autosome-enriched protein might repress genes on the X chromosome, promote PGC proliferation and survival, and influence the germ versus soma distinction...
  13. pmc MES-4: an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in the C. elegans germ line
    Laurel B Bender
    Department of Biology, Indiana University, Bloomington, IN 47405, USA
    Development 133:3907-17. 2006
    ..We discuss how an autosomally associated HMT may participate in silencing genes on the X chromosome, in coordination with the direct silencing effects of the other MES proteins...
  14. pmc Subunit contributions to histone methyltransferase activities of fly and worm polycomb group complexes
    Carrie S Ketel
    Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, 55455, USA
    Mol Cell Biol 25:6857-68. 2005
    ..Thus, although the fly and mammalian PcG complexes absolutely require SU(Z)12, the worm complex generates HMTase activity from a distinct partner set...
  15. pmc Genetic analysis of the Caenorhabditis elegans GLH family of P-granule proteins
    Caroline Spike
    Department of Biology, Indiana University, Bloomington, Indiana 47405, USA
    Genetics 178:1973-87. 2008
    ..We discuss the evolution of the Vasa/GLH genes and current views of their functions and the assembly and roles of germ granules among species...
  16. pmc DEPS-1 promotes P-granule assembly and RNA interference in C. elegans germ cells
    Caroline A Spike
    Department of Biology, Indiana University, Bloomington, IN 47405, USA
    Development 135:983-93. 2008
    ....
  17. pmc A genomewide RNAi screen for genes that affect the stability, distribution and function of P granules in Caenorhabditis elegans
    Dustin L Updike
    Department of Molecular Cell and Developmental Biology, University of California, Santa Cruz, California 95064, USA
    Genetics 183:1397-419. 2009
    ..Our findings strengthen the emerging view that germ granules are involved in numerous aspects of RNA metabolism, including an endo-siRNA pathway in germ cells...
  18. pmc A mutation of cdc-25.1 causes defects in germ cells but not in somatic tissues in C. elegans
    Jiyoung Kim
    Department of Bioscience and Biotechnology, Bio Molecular Informatics Center, Konkuk University, Seoul 143 701, Korea
    Mol Cells 28:43-8. 2009
    ..1 is expressed predominantly, if not exclusively, in the germ line during postembryonic stages. Our findings indicate that the function of cdc-25.1 is unique in the germ line but likely redundant with other members in the soma...
  19. pmc A germline-specific isoform of eIF4E (IFE-1) is required for efficient translation of stored mRNAs and maturation of both oocytes and sperm
    Melissa A Henderson
    Department of Biochemistry, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA
    J Cell Sci 122:1529-39. 2009
    ..Thus, IFE-1 plays independent roles in late oogenesis and spermatogenesis through selective translation of germline-specific mRNAs...
  20. pmc Vesicles and actin are targeted to the cleavage furrow via furrow microtubules and the central spindle
    Roger Albertson
    Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA
    J Cell Biol 181:777-90. 2008
    ..Transport of F-actin-associated vesicles on furrow MTs and the central spindle is thus an important mechanism by which actin and membrane are delivered to the cleavage furrow...
  21. pmc Functional analysis of cytoplasmic dynein heavy chain in Caenorhabditis elegans with fast-acting temperature-sensitive mutations
    Diane J Schmidt
    Department of Biology, Indiana University, Bloomington, IN 47405, USA
    Mol Biol Cell 16:1200-12. 2005
    ..This suggests that temperature-sensitive mutations can be created for time-resolved function analyses of dyneins and perhaps other P-loop proteins in a variety of model systems...