Time-keeping mechanisms of embryonic cell cycles

摘要 在胚胎发育过程中，身体的每一部分都被编程为包含一个准确的数字和安排 信元这种准确性是通过精确调节细胞增殖来实现的。这个项目的首要目标是 这项研究的目的是揭示果蝇胚胎发育过程中细胞周期精确控制的机制。 发展我们将研究形态发生中细胞周期调控的三个基本问题， 以下目标。在目标1中，我们将研究生物化学和机械信号的相互作用如何确保 精确的核定位具体来说，我们将讨论细胞周期振荡器的活动和 微管细胞骨架被整合以控制核向胚胎皮层的迁移。在目标2中，我们将研究 核质比如何通过激活DNA复制检查点来控制细胞周期 和合子基因组激活。我们还将研究反馈机制，通过该机制，细胞周期和 合子表达相互影响并确保母体到合子的稳健转变。在目标3中，我们 阐明cdc25string的转录调控如何确保有丝分裂时间的精确调控， 原肠胚形成我们还将研究控制有丝分裂域的背侧的机制， 胚胎，其中它们直接与十肢麻痹（Dpp）形态发生梯度的动态相关。 总的来说，我们的实验将确定一个定量框架，阐明细胞周期是如何调节的 在胚胎发育过程中。

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.