John S Satterlee et al. (2005) International Worm Meeting ""My favorite gene has a C. elegans homolog, please help me!""

Bethan Peach, Anne C Hart, Adriana K Jones, John S Satterlee, Jessica Koranda

[International Worm Meeting, 2005]

Many of us have heard the above request from colleagues who hope to employ the C. elegans model system to answer biological questions. The C. elegans Core Facility at MGH Cancer Center helps non-nematode researchers utilize C. elegans to investigate many different genes and biological questions. Our experiences have taught us valuable lessons, and required us to develop strategies for dealing with common problems. For example, which gene is the authentic C. elegans ortholog? What useful reagents and strains are available and how can they best be utilized? What is the most efficient way to identify an RNAi phenotype? Can we identify a panel of GFP-expressing strains to facilitate identification of tissue/cell specific RNAi phenotypes? What is the best way to characterize a deletion mutant? We will describe some of our successes in answering these questions using examples from our work investigating synMuv genes and other cancer-related signaling pathways.

R Mako Saito et al. (2004) East Coast Worm Meeting "cdc-14 regulates cki-1 to control cell-cycle arrest"

John S Satterlee, Audrey Perreault, Bethan Peach, Sander Van Den Heuvel, R Mako Saito

[East Coast Worm Meeting, 2004]

The development of multicellular organisms requires proper temporal and spatial control of cell divisions. To reveal underlying mechanisms, we screened for cell-cycle mutants that disrupt the reproducible pattern of somatic divisions in the nematode C. elegans . The screen for mutations that allowed extra divisions of the vulva precursor cells (VPC) led to the identification of genes that are required for their developmental arrest. Surprisingly, we found a novel role for the cdc-14 phosphatase in establishing the temporary quiescence of the VPCs. While budding yeast Cdc14p is essential for mitotic exit, inactivation of C. elegans cdc-14 resulted in extra cell divisions within multiple lineages, with no apparent defects in mitosis or cell-fate determination. The localization of a functional CDC-14 reporter was dynamic and cell-cycle dependent. Several lines of genetic evidence suggest that loss of cdc-14 function disrupts a cki-1 dependent pathway to arrest cell divisions during development. Moreover, we show that cdc-14 acts upstream of cki-1 and elevates CKI-1 nuclear accumulation. These data demonstrate that cdc-14 contributes to developmental regulation of cell-cycle arrest by promoting cki-1 activity. If conserved, a role for Cdc14 in Cip/Kip stabilization may have important implications for human cancer.

R Mako Saito et al. (2004) West Coast Worm Meeting "cdc-14 regulates cki-1 to control cell-cycle arrest"

Audrey Perreault, John S Satterlee, Bethan Peach, Sander Van Den Heuvel, R Mako Saito

[West Coast Worm Meeting, 2004]

The development of multicellular organisms requires proper temporal and spatial control of cell divisions. To reveal underlying mechanisms, we screened for cell-cycle mutants that disrupt the reproducible pattern of somatic divisions in the nematode C. elegans . The screen for mutations that allowed extra divisions of the vulva precursor cells (VPC) led to the identification of genes that are required for their developmental arrest. Surprisingly, we found a novel role for the cdc-14 phosphatase in establishing the temporary quiescence of the VPCs. While budding yeast Cdc14p is essential for mitotic exit, inactivation of C. elegans cdc-14 resulted in extra cell divisions within multiple lineages, with no apparent defects in mitosis or cell-fate determination. The localization of a functional CDC-14 reporter was dynamic and cell-cycle dependent. Several lines of genetic evidence suggest that loss of cdc-14 function disrupts a cki-1 dependent pathway to arrest cell divisions during development. Moreover, we show that cdc-14 acts upstream of cki-1 and elevates CKI-1 nuclear accumulation. These data demonstrate that cdc-14 contributes to developmental regulation of cell-cycle arrest by promoting cki-1 activity. If conserved, a role for cdc-14 in Cip/Kip stabilization may have important implications for human cancer.