Time-keeping mechanisms of embryonic cell cycles

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ABSTRACT During embryonic development each body part is programmed to contain an accurate number and arrangement of cells. This accuracy is achieved through precise regulation of cell proliferation. The overarching goal of this proposal is to reveal the mechanisms that ensure accurate control of the cell cycle during Drosophila embryonic development. We will study three fundamental questions of cell cycle regulation in morphogenesis by addressing the following Aims. In Aim 1, we will study how the interplay of biochemical and mechanical signals ensures accurate nuclear positioning. Specifically, we will address how the activity of the cell cycle oscillator and microtubule cytoskeleton are integrated to control nuclear migration to the embryo cortex. In Aim 2, we will study how the nuclear-to-cytoplasmic ratio controls the cell cycle via the activation of the DNA replication checkpoint and zygotic genome activation. We will also investigate the feedback mechanisms by which the cell cycle and zygotic expression influence each other and ensure a robust maternal-to-zygotic transition. In Aim 3, we will elucidate how transcriptional regulation of cdc25string ensures precise regulation of the timing of mitosis during gastrulation. We will also investigate the mechanisms controlling mitotic domains on the dorsal side of the embryos, where they are directly linked to the dynamic of the Decapentaplegic (Dpp) morphogen gradients. Collectively, our experiments will define a quantitative framework elucidating how the cell cycle is regulated accurately during embryonic development.