Error Correction in Early Embryos

项目摘要 该项目的长期目标是了解胚胎在早期发育过程中如何预防和纠正错误。 使他们能够在挑战中正常发展。它集中在两个方面的早期 胚胎错误校正，并使用斑马鱼作为脊椎动物模型。第一，胚胎如何应对和 从DNA损伤中恢复吗以前的工作确定了一种新的基因表达程序，似乎是一种新的基因表达程序。 对早期胚胎中DNA损伤的反应。实验将确定激活的条件 这个程序，激活后细胞会发生什么，以及每个基因在程序中扮演的角色。第二、 胚胎如何从不正确的模式中恢复？斜视突变胚胎最初的模式太少 由于Nodal信号减少，它们在原肠胚形成过程中纠正了它们的模式， 转化为正常的成年人实验将测试模式是如何在这些突变体中扩展的， 拯救的细胞来源于，然后应用单细胞RNAseq来确定校正的细胞是否不同 长期从野生型细胞。这些目标将显示胚胎中用于纠正模式错误的机制 并对DNA损伤做出反应，并确定错误纠正是否会在DNA中留下持久的差异。 胚胎最后，这些数据将阐明某些扰动如何导致部分渗透出生 缺陷和潜在的建议方法，以减少他们的反射率。

PROJECT ABSTRACT The long-term goal of this project is to understand how embryos prevent and correct errors during early development, enabling them to develop normally in spite of challenges. It focuses on two aspects of early embryonic error correction, and uses zebrafish as a vertebrate model. First, how do embryos respond to and recover from DNA damage? Previous work identified a novel gene expression program that seems to be a response to DNA damage specifically in early embryos. Experiments will identify the conditions that activate this program, what happens to cells after its activation, and the role each gene plays in the program. Second, how do embryos recover from improper patterning? squint mutant embryos initially pattern too little mesendoderm due to reduced Nodal signaling, but they correct their patterning during gastrulation and develop into phenotypically normal adults. Experiments will test how patterning is extended in these mutants, where the rescued cells originate from, and then apply single-cell RNAseq to determine whether corrected cells differ long-term from wild-type cells. These aims will show mechanisms used in embryos to correct patterning errors and respond to DNA damage, and determine whether error correction leaves persistent differences in the embryo. Lastly, these data will shed light on how some perturbations could result in partially penetrant birth defects and potentially suggest methods to reduce their penetrance.