Characterization of DAF-18/PTEN’s Role in Survival and Cellular Proliferation During Larval Arrest in Caenorhabditis elegans

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Zanetti, Michael
The role of insulin/IGF signaling (IIS) in regulating longevity and dauer formation in C. elegans is well defined. However, the role of IIS in stress responses such as L1 arrest is less studied and poorly understood. One of the regulators of longevity and lifespan in the worm is the homolog of the human tumour suppressor PTEN, called DAF- 18 in C. elegans. DAF-18 is known to act through the IIS pathway to regulate longevity, lifespan, dauer formation and also control germline proliferation during L1 arrest. I show that daf-18 mutants cannot properly L1 arrest and that the arrest phenotype is only partially rescued by IIS genes, indicating regulation of L1 arrest independent of the IIS pathway. Additionally, I identify a germline role for DAF-18/PTEN during L1 arrest. EMS mutagenesis screens were performed to find unbiased suppressors and worm homologs of candidate human cancer genes were tested for suppression of the L1 arrest phenotype. Finally, I show that in addition to controlling germline proliferation during arrest, DAF-18/PTEN controls divisions of some somatic tissues during L1 arrest, including in the muscle cell lineage and the mechanosensory neuron cell lineage.
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