Zinc is a transition metal that plays a role in an array of cellular processes and has traditionally been considered a cofactor and structural regulator. We propose a novel and unprecedented role for zinc as regulator in inorganic cell signaling. Studies from the O'Halloran and Woodruff labs have demonstrated that zinc regulates meiotic progression in mouse oocytes through massive zinc fluxes and association of zinc with the zinc-finger binding protein Emi2. The discovery that zinc is a master regulator of cell cycle progression has the potential to broadly impact the study of human disease, as extreme levels of zinc present in our cells can negatively affect cell division. We are expanding studies into Caenorhabditis elegans, to exploit their short reproductive lifespan, high number of offspring and translucence. It is unknown if zinc master regulation is a conserved cell signaling mechanism in C. elegans. Therefore, the proposed aims will fill this knowledge gap and identify how the zinc regulated cell signaling pathway defines the developing germline. We will achieve this goal by quantifying total and labile zinc within the gonad, test mechanisms of zinc switching events to define different regions of the gonad and identify the molecular mechanism of master zinc regulation of the Notch signaling pathway. These experiments will be conducted under zinc deficient conditions compared to controls. Information acquired from these studies will advance the knowledge base in zinc as a cell signaling regulator and lead to further understanding how zinc regulates cell cycle and thus germ cell identity, which is crucial for the development of new offspring.
Our project investigates zinc regulation of the developing germline and embryos in Caenorhabditis elegans. Our approach involves creating a zinc deficient environment, to study cell cycle aberrations, abnormal germline structure and embryo development.
|Mendoza, Adelita D; Woodruff, Teresa K; Wignall, Sarah M et al. (2017) Zinc availability during germline development impacts embryo viability in Caenorhabditis elegans. Comp Biochem Physiol C Toxicol Pharmacol 191:194-202|