A Molecular Genetic Analysis of Root Morphogenesis

发育生物学的一个中心问题是“细胞如何从多能进化而来？” 干细胞分化成完全分化的组织。干细胞不对称分裂以提供 以不同的轨迹发射的子代。在每个轨迹上，细胞通过 通过不同的状态进行终末分化。确实有 令人惊讶的是，制定了整个过程的案例很少，而且有 没有理解整个过程的规则的案例。关于这个问题的答案 问题是再生医学和发育疾病治疗的核心 精神错乱。我们使用拟南芥的根作为一个易于处理的模型来解决这个问题。 通过比较和对比动物和植物的分化途径，我们可以 理解它们的基本逻辑，因为它们是完全独立进化的。我们的 工作已经确定了该部门所需的核心分子网络和 一个干细胞群体的分化。该网络的数学建模 产生了关于它如何发挥作用的假设。我们现在正在试验性地测试 假设以及实时成像网络动态。我们还确认了 这一谱系中分化的关键调节因子。这些调控因子的异位表达 提供了对细胞命运的稳定性和获取细胞的要求的见解 命运。我们在表征干细胞到分化组织的路径方面的进展 Root将使我们能够解决基本问题，包括：“如何形成 不对称细胞分裂受调控吗？“以及“是什么控制了差异化？”致信地址 这些问题，我们将使用光学薄片显微镜的实时成像 细胞不对称分裂和单细胞全基因组表达分析 获取细胞命运。要充分了解控制这些的网络主题 我们将使用合成组件对流程进行重新设计。观测网 多细胞生物体中的动力学是一种独特的方法，它有可能 告知有关网络在其他生物过程中的作用的基本问题。 生成与数学建模相结合的合成网络主题将提供 对控制发展的监管网络的逻辑以及 转化为扰乱它们的疾病过程。

A central question in developmental biology is, “How do cells progress from pluripotent stem cells to fully differentiated tissues.” Stem cells divide asymmetrically to give daughters that are launched on different trajectories. On each trajectory, cells pass through different states as they progress toward end-stage differentiation. There are surprisingly few cases in which this whole process has been mapped out and there are no cases in which the regulation of the entire process is understood. Answers to this question lie at the heart of regenerative medicine and treatment of developmental disorders. We address this question using the root of Arabidopsis as a tractable model. Comparing and contrasting pathways to differentiation in animals and plants allows us to understand their underlying logic, as these evolved completely independently. Our work has identified the core molecular network required for the division and differentiation of one stem cell population. Mathematical modeling of this network generated hypotheses as to how it functions. We are now experimentally testing those hypotheses as well as imaging network dynamics in real time. We have also identified key regulators of differentiation in this lineage. Ectopic expression of these regulators provided insights into the stability of cell fate and the requirements for acquiring cell fate. Our progress in characterizing the path from stem cell to differentiated tissue in the root will allow us to address fundamental questions including, “How are formative asymmetric cell divisions regulated?” and “What controls differentiation?” To address these questions, we will use real time imaging with light sheet microscopy during asymmetric cell divisions and single-cell genome-wide expression analysis during the acquisition of cell fate. To fully understand the network motifs controlling these processes we will reengineer them using synthetic components. Observing network dynamics in a multicellular organism is a unique approach and has the potential to inform basic questions regarding network function in other biological processes. Generating synthetic network motifs coupled with mathematical modeling will provide key insights into the logic of regulatory networks that control development as well as into disease processes that disrupt them.