Amini R.,Institute of Research in Immunology and Cancer |
Goupil E.,Institute of Research in Immunology and Cancer |
Labella S.,McGill University |
Zetka M.,McGill University |
And 7 more authors.
Journal of Cell Biology | Year: 2014
Cytokinesis generally produces two separate daughter cells, but in some tissues daughter nuclei remain connected to a shared cytoplasm, or syncytium, through incomplete cytokinesis. How syncytia form remains poorly understood. We studied syncytial formation in the Caenorhabditis elegans germline, in which germ cells connect to a shared cytoplasm core (the rachis) via intercellular bridges. We found that syncytial architecture initiates early in larval development, and germ cells become progressively interconnected until adulthood. The short Anillin family scaffold protein ANI-2 is enriched at intercellular bridges from the onset of germ cell specification, and ANI-2 loss resulted in destabilization of intercellular bridges and germ cell multinucleation defects. These defects were partially rescued by depleting the canonical Anillin ANI-1 or blocking cytoplasmic streaming. ANI-2 is also required for elastic deformation of the gonad during ovulation. We propose that ANI-2 promotes germ cell syncytial organization and allows for compensation of the mechanical stress associated with oogenesis by conferring stability and elasticity to germ cell intercellular bridges. © 2014 Amini et al.
Benkemoun L.,Institute of Research in Immunology and Cancer |
Descoteaux C.,Institute of Research in Immunology and Cancer |
Chartier N.T.,Institute of Research in Immunology and Cancer |
Chartier N.T.,Joseph Fourier University |
And 3 more authors.
Journal of Cell Biology | Year: 2014
Regulation of cell cycle duration is critical during development, yet the underlying molecular mechanisms are still poorly understood. The two-cell stage Caenorhabditis elegans embryo divides asynchronously and thus provides a powerful context in which to study regulation of cell cycle timing during development. Using genetic analysis and high-resolution imaging, we found that deoxyribonucleic acid (DNA) replication is asymmetrically regulated in the two-cell stage embryo and that the PAR-4 and PAR-1 polarity proteins dampen DNA replication dynamics specifically in the posterior blastomere, independently of regulators previously implicated in the control of cell cycle timing. Our results demonstrate that accurate control of DNA replication is crucial during C. elegans early embryonic development and further provide a novel mechanism by which PAR proteins control cell cycle progression during asynchronous cell division. © 2014 Benkemoun et al.
News Article | October 31, 2016
Existing chemotherapy approaches treat cancer by targeting cells that are actively multiplying and have a high metabolic rate. However, cancer stem cells can escape this targeting, leading to chemotherapy-resistant cancer and disease relapse. Researchers suspect that the microenvironment in which some cancer stem cells develop may give them protection from chemotherapy treatments. In research described this week in the JCI, a team of researchers led by Trang Hoang at the University of Montreal determined that pre-leukemic stem cells were less sensitive to current chemotherapy drugs. The team then developed a powerful screening method to identify drugs that more effectively target and kill these pre-cancerous cells. They determined that pre-leukemic stem cells were dependent upon specific features in the bone marrow environment for survival. By mimicking these features in a drug screening assay, the researchers were able to identify a compound called 2-methyoxyestradiol that reduced survival of pre-leukemic cells without affecting normal cells. Treatment with 2-methyoxyestradiol also reduced the development of leukemia in a mouse model. The use of this and similar stem cell-targeted screening assays may lead to identification of novel approaches for treating chemotherapy-resistant and relapsed cancer. Trang Hoang Institute of Research in Immunology and Cancer - University of Montreal email@example.com