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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Molecular Cytology Study Section (CTY)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University Bloomington
Schools of Arts and Sciences
United States
Zip Code
Kaneshiro, Kiyomi R; Strome, Susan (2017) Inheritance of protection from osmotic stress. Nat Cell Biol 19:151-152
Knutson, Andrew Kek?pa'a; Egelhofer, Thea; Rechtsteiner, Andreas et al. (2017) Germ Granules Prevent Accumulation of Somatic Transcripts in the Adult Caenorhabditis elegans Germline. Genetics 206:163-178
Goetsch, Paul D; Garrigues, Jacob M; Strome, Susan (2017) Loss of the Caenorhabditis elegans pocket protein LIN-35 reveals MuvB's innate function as the repressor of DREAM target genes. PLoS Genet 13:e1007088
Marceau, Aimee H; Felthousen, Jessica G; Goetsch, Paul D et al. (2016) Structural basis for LIN54 recognition of CHR elements in cell cycle-regulated promoters. Nat Commun 7:12301
Ahn, Jeong H; Rechsteiner, Andreas; Strome, Susan et al. (2016) A Conserved Nuclear Cyclophilin Is Required for Both RNA Polymerase II Elongation and Co-transcriptional Splicing in Caenorhabditis elegans. PLoS Genet 12:e1006227
Garrigues, Jacob M; Sidoli, Simone; Garcia, Benjamin A et al. (2015) Defining heterochromatin in C. elegans through genome-wide analysis of the heterochromatin protein 1 homolog HPL-2. Genome Res 25:76-88
Strome, Susan; Updike, Dustin (2015) Specifying and protecting germ cell fate. Nat Rev Mol Cell Biol 16:406-16
Rahman, Mohammad M; Munzig, Mandy; Kaneshiro, Kiyomi et al. (2015) Caenorhabditis elegans polo-like kinase PLK-1 is required for merging parental genomes into a single nucleus. Mol Biol Cell 26:4718-35
Latorre, Isabel; Chesney, Michael A; Garrigues, Jacob M et al. (2015) The DREAM complex promotes gene body H2A.Z for target repression. Genes Dev 29:495-500
Gaydos, Laura J; Wang, Wenchao; Strome, Susan (2014) Gene repression. H3K27me and PRC2 transmit a memory of repression across generations and during development. Science 345:1515-8

Showing the most recent 10 out of 64 publications