Research SummaryRelevance of State of Ploidy on Vertebrate Embryogenesis
In mammals, a diploid zygote is essential for viability as aneuploidy or polyploidy result in spontaneous abortions and lethal congenital abnormalities. My interest lies in understanding the cellular and molecular principles dictating this absolute requirement for diploidy in vertebrate embryogenesis, using zebrafish as a model organism.
Diploid zygotic nuclei are initially transcriptionally quiescent and begin transcription during a conserved developmental transition, the zygotic genome activation (ZGA). Altered ploidy is known to temporally alter ZGA, yet the exact mechanisms by which initial ploidy is sensed and how it impinges on ZGA is poorly understood. Our goal is to understand the molecular changes occurring as a result of altered ploidy in zebrafish embryos to uncover the developmental cause of mortality associated with non-diploidy and the mechanisms that control ZGA. Additionally, we are interested in understanding how cells interact with neighbours that have ploidy different from their own. This becomes interesting because in diploid embryos mosaic polyploidy is tolerated contextually (e.g. in the liver) and in certain disease states. It appears that cells have the ability to sense ploidy and adapt to it contextually however, the mechanisms behind this are unclear.
What is indeed clear is that the ability of the zygote and individual cells in a multicellular embryo to sense ploidy and adapt molecularly and cellularly is fundamental to organismal viability. Our work in zebrafish will further our understanding of the mechanistic basis for this sensing and adaptation during embryonic development and homeostasis.